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出境医 / 临床实验 / 联合或不联合Lestaurtinib的化学疗法治疗新诊断为急性淋巴细胞白血病的年轻患者
联合或不联合Lestaurtinib的化学疗法治疗新诊断为急性淋巴细胞白血病的年轻患者
Study Description
Brief Summary:
This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Lymphoblastic Leukemia Acute Undifferentiated Leukemia Childhood T Acute Lymphoblastic Leukemia Untreated Childhood Acute Lymphoblastic Leukemia | Drug: Asparaginase Drug: Cyclophosphamide Drug: Cytarabine Drug: Daunorubicin Hydrochloride Drug: Dexamethasone Drug: Etoposide Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: Lestaurtinib Drug: Leucovorin Calcium Drug: Mercaptopurine Drug: Methotrexate Drug: Methylprednisolone Drug: Pegaspargase Other: Pharmacological Study Drug: Prednisone Drug: Therapeutic Hydrocortisone Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 218 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807) |
| Actual Study Start Date : | January 14, 2008 |
| Actual Primary Completion Date : | September 30, 2017 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Arm A (standard risk MLL-G)
Population Description: Eligible patients with MLL-G (germline, or non-rearranged)
|
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies
Drug: Leucovorin Calcium Given IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone Given IV
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Other: Pharmacological Study Correlative studies
Drug: Prednisone Given PO
Other Names:
Drug: Therapeutic Hydrocortisone Given IT
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
|
|
Active Comparator: Arm B (IR/HR MLL-R chemotherapy)
Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.
|
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies
Drug: Leucovorin Calcium Given IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone Given IV
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Other: Pharmacological Study Correlative studies
Drug: Prednisone Given PO
Other Names:
Drug: Therapeutic Hydrocortisone Given IT
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
|
|
Experimental: Arm C (IR/HR MLL-R chemotherapy and lestaurtinib)
Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.
|
Drug: Asparaginase
Given IV, IM, or PO
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or IT
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Etoposide Given IV
Other Names:
Biological: Filgrastim Given IV or SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies
Drug: Lestaurtinib Given PO
Other Names:
Drug: Leucovorin Calcium Given IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IV, IT, or PO
Other Names:
Drug: Methylprednisolone Given IV
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Other: Pharmacological Study Correlative studies
Drug: Prednisone Given PO
Other Names:
Drug: Therapeutic Hydrocortisone Given IT
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures :
- Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) [ Time Frame: From start of post-induction therapy for up to 10 years ]EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Secondary Outcome Measures :
- Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 [ Time Frame: From start of post-induction therapy for up to 10 years. ]Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B.
- Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) [ Time Frame: Up to 12 weeks from start of induction ]Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients.
- Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Up to 12 weeks ]Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Up to 12 weeks ]Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Sampled between weeks 6-12 from start of induction ]Summarized with mean and standard deviation for those with available data in Arm C
- Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: Sampled at the start of induction ]Described via mean and standard deviation by group.
- Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: At relapse (up to 3 years) ]Described via means and standard deviations in available Arm C relapse samples
- Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: Sampled at the start of induction ]Described via means and standard deviations in samples which have primary resistance to lestaurtinib
- Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: At relapse (up to 3 years) ]Described via means and standard deviations in samples which have acquired resistance to lestaurtinib
- Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm [ Time Frame: 3 Years from end of Induction) ]Three-year EFS estimates an
Tracking Information First Submitted Date ICMJE November 9, 2007 First Posted Date ICMJE November 12, 2007 Results First Submitted Date ICMJE September 26, 2018 Results First Posted Date ICMJE December 10, 2018 Last Update Posted Date March 25, 2021 Actual Study Start Date ICMJE January 14, 2008 Actual Primary Completion Date September 30, 2017 (Final data collection date for primary outcome measure) Current Primary Outcome Measures ICMJE
Percent Probability for Event-free Survival (EFS) for Patients on Arm C at Dose Level 2 (DL2) [ Time Frame: From start of post-induction therapy for up to 10 years ] EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.Original Primary Outcome Measures ICMJE
Event-free survival at 3 years Change History Current Secondary Outcome Measures ICMJE
- Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 [ Time Frame: From start of post-induction therapy for up to 10 years. ]Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto. EFS will be compared between patients on treatment Arm C at DL2 to those on Arm B.
- Number of Patients Who Experienced Lestaurtinib-related Dose Limiting Toxicity (DLT) [ Time Frame: Up to 12 weeks from start of induction ]Lestaurtinib-related dose-limiting toxicity proportions, as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, will by summarized by dose level for Safety phase patients.
- Pharmacokinetic AGP Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Up to 12 weeks ]Pharmacokinetic AGP levels in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacokinetic Albumin in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Up to 12 weeks ]Pharmacokinetic albumin in infants given lestaurtinib at DL2 in combination with chemotherapy will be described with mean and standard deviation for those with available data.
- Pharmacodynamics PIA Levels in Infants Given Lestaurtinib at DL2 in Combination With Chemotherapy [ Time Frame: Sampled between weeks 6-12 from start of induction ]Summarized with mean and standard deviation for those with available data in Arm C
- Describe FLT3 Protein Expression as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: Sampled at the start of induction ]Described via mean and standard deviation by group.
- Describe FLT3 Protein Expression as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: At relapse (up to 3 years) ]Described via means and standard deviations in available Arm C relapse samples
- Describe in Vitro Sensitivity as a Molecular Mechanism of Primary Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: Sampled at the start of induction ]Described via means and standard deviations in samples which have primary resistance to lestaurtinib
- Describe in Vitro Sensitivity as a Molecular Mechanism of Acquired Resistance to Lestaurtinib in Leukemic Blasts [ Time Frame: At relapse (up to 3 years) ]Described via means and standard deviations in samples which have acquired resistance to lestaurtinib
- Percent Probability of Event Free Survival (EFS) by MRD Status and Treatment Arm [ Time Frame: 3 Years from end of Induction) ]Three-year EFS estimates and 90% CI will be reported by treatment arm and end-induction MRD status.
- Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With Survival Outcomes [ Time Frame: At 3 years ]EFS outcomes will be reported by genotype.
- Identification of Gene Expression Patterns in Diagnostic Infant Leukemia Samples That Correlate With PIA Values [ Time Frame: At 3 years ]Means and standard deviations of Plasma Inhibitory Activity (PIA) will be given by genotype
- Percent Probability for Event-free Survival (EFS) for Patients on Arm A [ Time Frame: From start of post-induction therapy for up to 10 years ]EFS time is defined as time from treatment assignment to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. EFS is constructed using the Kaplan-Meier life table method with confidence interval based on standard errors computed using the method of Peto and Peto.
Original Secondary Outcome Measures ICMJE
- Dose of lestaurtinib
- Pharmacokinetic and pharmacodynamic profile of lestaurtinib
- Molecular mechanisms of resistance to lestaurtinib in leukemic blasts
- Levels of minimal residual disease
- Gene expression patterns
- Outcome of infants with MLL-germline ALL treated with a modified chemotherapy backbone that includes an extended continuation phase
Current Other Pre-specified Outcome Measures Not Provided Original Other Pre-specified Outcome Measures Not Provided Descriptive Information Brief Title ICMJE Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Official Title ICMJE A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia (ALL): Randomization of Highest Risk Infants to Intensive Chemotherapy +/- FLT3 Inhibition (CEP-701, Lestaurtinib; NSC#617807) Brief Summary This phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia. Detailed Description PRIMARY OBJECTIVES:
I. To estimate the 3-year event-free survival (EFS) of infants with mixed lineage leukemia-rearranged (MLL-R) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus the fms-related tyrosine kinase 3 (FLT3) inhibitor lestaurtinib.
SECONDARY OBJECTIVES:
I. To compare the 3-year EFS of infants with MLL-R ALL treated with chemotherapy plus the FLT3 inhibitor lestaurtinib to MLL-R patients treated with chemotherapy alone.
II. To determine a safe, tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants.
III. To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy.
IV. To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts.
V. To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy, and correlate with outcome.
VI. To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy.
VII. To describe the outcome of infants with MLL-G ALL treated with a modified P9407 chemotherapy backbone that includes an extended continuation phase.
OUTLINE:
INDUCTION THERAPY (WEEKS 1-5): All patients receive induction therapy comprising vincristine sulfate intravenously (IV) over 1 minute on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over 30 minutes on days 8 and 9; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 (closed as of 05/19/09); pegaspargase or asparaginase intramuscularly (IM) on days 15, 18, 22, 25, 29, and 33; prednisone orally (PO) thrice daily (TID) or methylprednisolone IV on days 1-7; dexamethasone IV or PO TID on days 8-28; cytarabine IV over 30 minutes on days 8-21; methotrexate intrathecally (IT) on days 1 and 29; cytarabine IT on day 15; hydrocortisone IT on days 15 and 29; and filgrastim IV or subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. Standard-risk patients are non-randomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib (post-induction therapy A).
POST-INDUCTION THERAPY A: (for standard-risk patients MLL-germline [G])
INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 8; leucovorin calcium IV or PO every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is < 0.1 uM; cyclophosphamide IV over 30 minutes on days 15-19; etoposide IV over 2 hours on days 15-19; and filgrastim IV or SC beginning on day 20 and continuing until blood counts recover. Patients in morphologic remission proceed to re-induction therapy.
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; daunorubicin hydrochloride IV over 30 minutes on days 1 and 2; cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4; pegaspargase or asparaginase IM on day 4; dexamethasone IV or PO twice daily (BID) on days 1-7 and 15-21; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on days 1 and 15; and filgrastim IV or SC beginning on day 5 and continuing until blood counts recover.
CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8; leucovorin calcium IV every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is < 0.1 uM; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1; etoposide IV over 2 hours on days 15-19; cyclophosphamide IV over 30 minutes on days 15-19; high-dose cytarabine IV over 3 hours every 12 hours on days 29 and 30; pegaspargase or asparaginase IM on day 30; and filgrastim IV or SC beginning on day 20 and day 31 and continuing until blood counts recover.
CONTINUATION I (WEEKS 20-41): Patients receive vincristine sulfate IV on day 1 in weeks 20 and 24; dexamethasone IV or PO BID on days 1-5 in weeks 20, and 24; triple IT chemotherapy comprising methotrexate, cytarabine, and hydrocortisone on day 1 in weeks 20 and 24; methotrexate IV on day 1 in weeks 21-24 and 25-27; etoposide IV over 2 hours on day 1-5 in week 28; cyclophosphamide IV over 30 minutes on days 1-5 in week 28; mercaptopurine PO on days 1-7 in weeks 21-23 and 25-27; and filgrastim SC or IV beginning on day 6 in week 28 and continuing until blood counts recover.
CONTINUATION II (WEEKS 42-104): Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone IV or PO BID on days 1-5, 29-33, and 57-61; methotrexate IT on day 1; methotrexate PO on days 8, 15, 22, 36, 43, 50, 64, 71, and 78; and mercaptopurine PO on days 8-28, 36-56, and 64-84. Treatment repeats every 12 weeks for 2 years from diagnosis.
A safety/activity phase is conducted separately for the intermediate-risk (IR) and high-risk (HR) patients to identify a safe, tolerable, and biologically active dose of lestaurtinib combined with chemotherapy backbone. Once a tolerable/active dose of lestaurtinib has been identified for IR patients, subsequent IR patients are eligible to proceed to an efficacy phase, where they are randomized (or non-randomly assigned as of 7/16/2014) to chemotherapy with or without lestaurtinib. HR patients separately proceed to the randomized efficacy phase if a tolerable/active dose is identified for the HR stratum. IR and HR patients are randomized (or non-randomly assigned as of 7/16/2014) to 1 of 2 post-induction therapy regimens (post-induction therapy B or C).
POST-INDUCTION THERAPY B: (chemotherapy only for IR/HR patients classified as MLL-R; age >= 90 days at diagnosis):
INDUCTION INTENSIFICATION (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy A induction intensification. Patients in morphologic remission proceed to re-induction. (Retired as of 7/16/2014)
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy A re-induction. (Retired as of 7/16/2014)
CONSOLIDATION (WEEKS 13-19): Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy A consolidation. (Retired as of 7/16/2014)
CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate IV over 1 minute on day 1 in weeks 20, 24, 33, 37, and 46; dexamethasone PO or IV BID on days 1-5 in weeks 20, 24, 33, 37, and 46; triple IT chemotherapy on day 1 in weeks 20, 24, 33, 37, and 46; methotrexate IV on day 1 in weeks 21-23, 25-26 and 37-45; mercaptopurine PO on days 1-7 in weeks 21-23, 25-26 and 37-45; etoposide IV over 2 hours on days 1-5 in week 27; cyclophosphamide IV over 2 hours on days 1-5 in week 27: high-dose cytarabine IV over 3 hours every 12 hours on days 1 and 2 in week 30; pegaspargase or asparaginase IM on day 2 in week 30: and filgrastim SC or IV beginning on day 3 in weeks 30 and continuing until blood counts recover. (Retired as of 7/16/2014)
CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy A continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis. (Retired as of 7/16/2014)
POST-INDUCTION THERAPY C: (chemotherapy and lestaurtinib for IR/HR patients classified as MLL-R; age < 90 days at diagnosis)
INDUCTION INTENSIFICATION THERAPY (WEEKS 6-9): Patients receive high-dose methotrexate, leucovorin calcium, cyclophosphamide, etoposide, and filgrastim as in post-induction therapy B induction intensification. Patients also receive lestaurtinib PO BID on days 20-27. Patients in morphologic remission proceed to re-induction.
RE-INDUCTION (WEEKS 10-12): Patients receive vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, pegaspargase or asparaginase, dexamethasone, triple IT chemotherapy, and filgrastim as in post-induction therapy B re-induction. Patients also receive lestaurtinib PO on days 5-20.
CONSOLIDATION (WEEKS 13-19) Patients receive high-dose methotrexate, leucovorin calcium, triple IT chemotherapy, etoposide, cyclophosphamide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B consolidation. Patients also receive lestaurtinib PO on days 20-27 and 31-42.
CONTINUATION I (WEEKS 20-49): Patients receive vincristine sulfate, dexamethasone, triple IT chemotherapy, methotrexate, mercaptopurine, etoposide, high-dose cytarabine, pegaspargase or asparaginase, and filgrastim as in post-induction therapy B continuation I. Patients also receive lestaurtinib PO on days 2-6 in weeks 20 and 24; days 27-41 in weeks 27-29; days 45-56 in weeks 30-32.
CONTINUATION II (WEEKS 50-104): Patients receive vincristine sulfate, dexamethasone, IT methotrexate, methotrexate PO, and mercaptopurine PO as in post-induction therapy B continuation II. Treatment repeats every 12 weeks for 2 years from diagnosis.
After completion of study treatment, all patients are followed up every 1-6 months for 4 years and then annually thereafter.
Study Type ICMJE Interventional Study Phase ICMJE Phase 3 Study Design ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: TreatmentCondition ICMJE - Acute Lymphoblastic Leukemia
- Acute Undifferentiated Leukemia
- Childhood T Acute Lymphoblastic Leukemia
- Untreated Childhood Acute Lymphoblastic Leukemia
Intervention ICMJE - Drug: Asparaginase
Given IV, IM, or POOther Names:
- ASP-1
- Asparaginase II
- Asparaginase-E.Coli
- Colaspase
- Elspar
- Kidrolase
- L-Asnase
- L-ASP
- L-Asparaginase
- L-Asparagine amidohydrolase
- Laspar
- Lcf-ASP
- Leucogen
- Leunase
- MK-965
- Paronal
- Re-82-TAD-15
- Serasa
- Spectrila
- Drug: Cyclophosphamide
Given IVOther Names:
- (-)-Cyclophosphamide
- 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
- Carloxan
- Ciclofosfamida
- Ciclofosfamide
- Cicloxal
- Clafen
- Claphene
- CP monohydrate
- CTX
- CYCLO-cell
- Cycloblastin
- Cycloblastine
- Cyclophospham
- Cyclophosphamid monohydrate
- Cyclophosphamidum
- Cyclophosphan
- Cyclophosphane
- Cyclophosphanum
- Cyclostin
- Cyclostine
- Cytophosphan
- Cytophosphane
- Cytoxan
- Fosfaseron
- Genoxal
- Genuxal
- Ledoxina
- Mitoxan
- Neosar
- Revimmune
- Syklofosfamid
- WR- 138719
- Drug: Cytarabine
Given IV or ITOther Names:
- .beta.-Cytosine arabinoside
- 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
- 1-.beta.-D-Arabinofuranosylcytosine
- 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
- 1-Beta-D-arabinofuranosylcytosine
- 1.beta.-D-Arabinofuranosylcytosine
- 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
- Alexan
- Ara-C
- ARA-cell
- Arabine
- Arabinofuranosylcytosine
- Arabinosylcytosine
- Aracytidine
- Aracytin
- Aracytine
- Beta-cytosine Arabinoside
- CHX-3311
- Cytarabinum
- Cytarbel
- Cytosar
- Cytosine Arabinoside
- Cytosine-.beta.-arabinoside
- Cytosine-beta-arabinoside
- Erpalfa
- Starasid
- Tarabine PFS
- U 19920
- U-19920
- Udicil
- WR-28453
- Drug: Daunorubicin Hydrochloride
Given IVOther Names:
- Cerubidin
- Cerubidine
- Cloridrato de Daunorubicina
- Daunoblastin
- Daunoblastina
- Daunoblastine
- Daunomycin Hydrochloride
- Daunomycin, hydrochloride
- Daunorubicin.HCl
- Daunorubicini Hydrochloridum
- FI-6339
- Ondena
- RP-13057
- Rubidomycin Hydrochloride
- Rubilem
- Drug: Dexamethasone
Given IV or POOther Names:
- Aacidexam
- Adexone
- Aknichthol Dexa
- Alba-Dex
- Alin
- Alin Depot
- Alin Oftalmico
- Amplidermis
- Anemul mono
- Auricularum
- Auxiloson
- Baycuten
- Baycuten N
- Cortidexason
- Cortisumman
- Decacort
- Decadrol
- Decadron
- Decalix
- Decameth
- Decasone R.p.
- Dectancyl
- Dekacort
- Deltafluorene
- Deronil
- Desamethasone
- Desameton
- Dexa-Mamallet
- Dexa-Rhinosan
- Dexa-Scheroson
- Dexa-sine
- Dexacortal
- Dexacortin
- Dexafarma
- Dexafluorene
- Dexalocal
- Dexamecortin
- Dexameth
- Dexamethasonum
- Dexamonozon
- Dexapos
- Dexinoral
- Dexone
- Dinormon
- Fluorodelta
- Fortecortin
- Gammacorten
- Hexadecadrol
- Hexadrol
- Lokalison-F
- Loverine
- Methylfluorprednisolone
- Millicorten
- Mymethasone
- Orgadrone
- Spersadex
- Visumetazone
- Drug: Etoposide
Given IVOther Names:
- Demethyl Epipodophyllotoxin Ethylidine Glucoside
- EPEG
- Lastet
- Toposar
- Vepesid
- VP 16-213
- VP-16
- VP-16-213
- Biological: Filgrastim
Given IV or SCOther Names:
- FILGRASTIM, LICENSE HOLDER UNSPECIFIED
- G-CSF
- Neupogen
- r-metHuG-CSF
- Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
- rG-CSF
- Tevagrastim
- Other: Laboratory Biomarker Analysis
Correlative studies
- Drug: Lestaurtinib
Given POOther Names:
- CEP-701
- KT-5555
- SPM-924
- Drug: Leucovorin Calcium
Given IVOther Names:
- Adinepar
- Calcifolin
- Calcium (6S)-Folinate
- Calcium Folinate
- Calcium Leucovorin
- Calfolex
- Calinat
- Cehafolin
- Citofolin
- Citrec
- citrovorum factor
- Cromatonbic Folinico
- Dalisol
- Disintox
- Divical
- Ecofol
- Emovis
- Factor, Citrovorum
- Flynoken A
- Folaren
- Folaxin
- FOLI-cell
- Foliben
- Folidan
- Folidar
- Folinac
- Folinate Calcium
- folinic acid
- Folinic Acid Calcium Salt Pentahydrate
- Folinoral
- Folinvit
- Foliplus
- Folix
- Imo
- Lederfolat
- Lederfolin
- Leucosar
- leucovorin
- Rescufolin
- Rescuvolin
- Tonofolin
- Wellcovorin
- Drug: Mercaptopurine
Given POOther Names:
- 3H-Purine-6-thiol
- 6 MP
- 6 Thiohypoxanthine
- 6 Thiopurine
- 6-Mercaptopurine
- 6-Mercaptopurine Monohydrate
- 6-MP
- 6-Purinethiol
- 6-Thiopurine
- 6-Thioxopurine
- 6H-Purine-6-thione, 1,7-dihydro- (9CI)
- 7-Mercapto-1,3,4,6-tetrazaindene
- Alti-Mercaptopurine
- Azathiopurine
- BW 57-323H
- Flocofil
- Ismipur
- Leukerin
- Leupurin
- Mercaleukim
- Mercaleukin
- Mercaptina
- Mercaptopurinum
- Mercapurin
- Mern
- NCI-C04886
- Puri-Nethol
- Purimethol
- Purine, 6-mercapto-
- Purine-6-thiol (8CI)
- Purine-6-thiol, monohydrate
- Purinethiol
- Purinethol
- U-4748
- WR-2785
- Drug: Methotrexate
Given IV, IT, or POOther Names:
- Abitrexate
- Alpha-Methopterin
- Amethopterin
- Brimexate
- CL 14377
- CL-14377
- Emtexate
- Emthexat
- Emthexate
- Farmitrexat
- Fauldexato
- Folex
- Folex PFS
- Lantarel
- Ledertrexate
- Lumexon
- Maxtrex
- Medsatrexate
- Metex
- Methoblastin
- Methotrexate LPF
- Methotrexate Methylaminopterin
- Methotrexatum
- Metotrexato
- Metrotex
- Mexate
- Mexate-AQ
- MTX
- Novatrex
- Rheumatrex
- Texate
- Tremetex
- Trexeron
- Trixilem
- WR-19039
- Drug: Methylprednisolone
Given IVOther Names:
- Adlone
- Caberdelta M
- DepMedalone
- Depo Moderin
- Depo-Nisolone
- Duralone
- Emmetipi
- Esametone
- Firmacort
- Medlone 21
- Medrate
- Medrol
- Medrol Veriderm
- Medrone
- Mega-Star
- Meprolone
- Methylprednisolonum
- Metilbetasone Solubile
- Metrocort
- Metypresol
- Metysolon
- Predni-M-Tablinen
- Prednilen
- Radilem
- Sieropresol
- Solpredone
- Summicort
- Urbason
- Veriderm Medrol
- Wyacort
- Drug: Pegaspargase
Given IMOther Names:
- L-Asparaginase with Polyethylene Glycol
- Oncaspar
- PEG-Asparaginase
- PEG-L-Asparaginase
- PEG-L-Asparaginase (Enzon - Kyowa Hakko)
- PEGLA
- Polyethylene Glycol L-Asparaginase
- Polyethylene Glycol-L-Asparaginase
- Other: Pharmacological Study
Correlative studies
- Drug: Prednisone
Given POOther Names:
- .delta.1-Cortisone
- 1, 2-Dehydrocortisone
- Adasone
- Cortancyl
- Dacortin
- DeCortin
- Decortisyl
- Decorton
- Delta 1-Cortisone
- Delta-Dome
- Deltacortene
- Deltacortisone
- Deltadehydrocortisone
- Deltasone
- Deltison
- Deltra
- Econosone
- Lisacort
- Meprosona-F
- Metacortandracin
- Meticorten
- Ofisolona
- Orasone
- Panafcort
- Panasol-S
- Paracort
- PRED
- Predicor
- Predicorten
- Prednicen-M
- Prednicort
- Prednidib
- Prednilonga
- Predniment
- Prednisonum
- Prednitone
- Promifen
- Servisone
- SK-Prednisone
- Drug: Therapeutic Hydrocortisone
Given ITOther Names:
- Aeroseb-HC
- Barseb HC
- Barseb-HC
- Cetacort
- Cort-Dome
- Cortef
- Cortenema
- Cortifan
- Cortisol
- Cortispray
- Cortril
- Dermacort
- Domolene
- Eldecort
- Hautosone
- Heb-Cort
- HYDROCORTISONE
- Hydrocortone
- Hytone
- Komed-HC
- Nutracort
- Proctocort
- Rectoid
- Drug: Vincristine Sulfate
Given IVOther Names:
- Kyocristine
- Leurocristine sulfate
- Leurocristine, sulfate
- Oncovin
- Vincasar
- Vincosid
- Vincrex
- Vincristine, sulfate
Study Arms ICMJE - Experimental: Arm A (standard risk MLL-G)
Population Description: Eligible patients with MLL-G (germline, or non-rearranged)Interventions:
- Drug: Asparaginase
- Drug: Cyclophosphamide
- Drug: Cytarabine
- Drug: Daunorubicin Hydrochloride
- Drug: Dexamethasone
- Drug: Etoposide
- Biological: Filgrastim
- Other: Laboratory Biomarker Analysis
- Drug: Leucovorin Calcium
- Drug: Mercaptopurine
- Drug: Methotrexate
- Drug: Methylprednisolone
- Drug: Pegaspargase
- Other: Pharmacological Study
- Drug: Prednisone
- Drug: Therapeutic Hydrocortisone
- Drug: Vincristine Sulfate
- Active Comparator: Arm B (IR/HR MLL-R chemotherapy)
Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.Interventions:
- Drug: Asparaginase
- Drug: Cyclophosphamide
- Drug: Cytarabine
- Drug: Daunorubicin Hydrochloride
- Drug: Dexamethasone
- Drug: Etoposide
- Biological: Filgrastim
- Other: Laboratory Biomarker Analysis
- Drug: Leucovorin Calcium
- Drug: Mercaptopurine
- Drug: Methotrexate
- Drug: Methylprednisolone
- Drug: Pegaspargase
- Other: Pharmacological Study
- Drug: Prednisone
- Drug: Therapeutic Hydrocortisone
- Drug: Vincristine Sulfate
- Experimental: Arm C (IR/HR MLL-R chemotherapy and lestaurtinib)
Population Description: Eligible patients with MLL-R (rearranged). Considered Intermediate Risk (IR) if age >= 90 days at diagnosis and High Risk (HR) if age < 90 days at diagnosis.Interventions:
- Drug: Asparaginase
- Drug: Cyclophosphamide
- Drug: Cytarabine
- Drug: Daunorubicin Hydrochloride
- Drug: Dexamethasone
- Drug: Etoposide
- Biological: Filgrastim
- Other: Laboratory Biomarker Analysis
- Drug: Lestaurtinib
- Drug: Leucovorin Calcium
- Drug: Mercaptopurine
- Drug: Methotrexate
- Drug: Methylprednisolone
- Drug: Pegaspargase
- Other: Pharmacological Study
- Drug: Prednisone
- Drug: Therapeutic Hydrocortisone
- Drug: Vincristine Sulfate
Publications * Loftus JP, Yahiaoui A, Brown PA, Niswander LM, Bagashev A, Wang M, Schauf A, Tannheimer S, Tasian SK. Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia. Haematologica. 2021 Apr 1;106(4):1067-1078. doi: 10.3324/haematol.2019.241729.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.Recruitment Information Recruitment Status ICMJE Active, not recruiting Actual Enrollment ICMJE
218 Original Enrollment ICMJE
244 Study Completion Date ICMJE Not Provided Actual Primary Completion Date September 30, 2017 (Final data collection date for primary outcome measure) Eligibility Criteria ICMJE Inclusion Criteria:
- Patients must be enrolled on a Children's Oncology Group (COG) ALL Classification Study (AALL08B1) prior to enrollment on AALL0631
- Patients must be newly diagnosed with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL); patients with T-cell ALL are eligible; patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominately lymphoid
- Patients with mature B-cell ALL or acute myelogenous leukemia (AML) are NOT eligible
- Patients with Down syndrome are NOT eligible
- Patients must be previously untreated with the exception of steroids and intrathecal chemotherapy; no other systemic chemotherapy may have been administered; patients receiving prior steroid therapy are eligible for study; any amount of steroid pretreatment will not affect initial induction assignment as long as the patient meets all other eligibility criteria; IT chemotherapy per protocol is allowed for patient convenience at the time of the diagnostic bone marrow or venous line placement to avoid second lumbar puncture; (note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Sex/Gender ICMJE Sexes Eligible for Study: All Ages ICMJE up to 1 Year (Child) Accepts Healthy Volunteers ICMJE No Contacts ICMJE Contact information is only displayed when the study is recruiting subjects Listed Location Countries ICMJE Australia, Canada, New Zealand, United States Removed Location Countries Israel Administrative Information NCT Number ICMJE NCT00557193 Other Study ID Numbers ICMJE AALL0631
NCI-2009-00313 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AALL0631
08-146
CDR0000573996
AALL0631 ( Other Identifier: Childrens Oncology Group )
AALL0631 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )Has Data Monitoring Committee Yes U.S. FDA-regulated Product Not Provided IPD Sharing Statement ICMJE Not Provided Responsible Party Children's Oncology Group Study Sponsor ICMJE Children's Oncology Group Collaborators ICMJE National Cancer Institute (NCI) Investigators ICMJE Principal Investigator: Joanne Hilden Children's Oncology Group PRS Account Children's Oncology Group Verification Date March 2021
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP - Percent Probability for Event-free Survival (EFS) of MLL-R Infants Treated With Combination Chemotherapy With or Without Lestaurtinib at DL2 [ Time Frame: From start of post-induction therapy for up to 10 years. ]
治疗案例
- 希瑟·沃尔特斯-病人故事
- 凯西头血癌的故事成人急性淋巴细胞白血病（全部）
- 威廉·扬克（William Yank）血液癌故事，急性淋巴细胞白血病，B型细胞
- Veronica Balanza白血病的故事急性淋巴细胞白血病，B细胞，PH-
- 埃文·莱丝勒（Evan Lessler）血液癌故事讲述成人急性淋巴细胞白血病（ALL）
- 克里斯汀·米尔斯（Christine Mills）白血病故事：急性淋巴细胞白血病，T细胞
- 西亚拉·托特（Ciara Toth）血癌故事讲述急性淋巴细胞白血病
- 萨沙塔诺里（Sasha Tanori）的血液癌故事说明了急性髓细胞性白血病（AML）
- 莱斯利·泰瑟（Leslie Tysseling）的血癌故事讲述急性早幼粒细胞白血病（APL）
- 路易莎·里昂（Luisa Lyons）血液癌症故事讲述急性髓性白血病，Flit 3突变