Condition or disease | Intervention/treatment | Phase |
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Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia | Drug: Cytarabine Drug: Cytarabine Hydrochloride Drug: Etoposide Drug: Etoposide Phosphate Drug: Mitoxantrone Drug: Mitoxantrone Hydrochloride Drug: Peposertib | Phase 1 |
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability and determine the recommended phase two dose (RP2D) of M3814 in combination with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To characterize the pharmacokinetic (PK) profile of MEC alone and of M3814 in combination with MEC.
II. To evaluate the preliminary efficacy of M3814 in combination with MEC in patients with R/R AML as measured by the response rate (complete remission [CR] plus CR with incomplete count recovery), duration of CR/CRi (DOR), event-free survival (EFS) and overall survival (OS).
EXPLORATORY OBJECTIVES:
I. To evaluate correlative biomarkers of M3814 target engagement and response. II. To correlate cytogenetic and molecular abnormalities with response. III. To evaluate the rates of early mortality and allogeneic hematopoietic cell transplantation.
IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to:
IVa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned.
IVb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms.
V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome.
OUTLINE: This is a dose-escalation study of M3814.
Patients receive M3814 orally (PO) twice daily (BID) on days 2-21, mitoxantrone intravenously (IV) over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months thereafter.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 48 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1 Study of M3814 in Combination With MEC in Patients With Relapsed or Refractory Acute Myeloid Leukemia |
Actual Study Start Date : | October 4, 2019 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | December 31, 2021 |
Arm | Intervention/treatment |
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Experimental: Treatment (M3814, mitoxantrone, etoposide, cytarabine)
Patients receive M3814 PO BID on days 2-21, mitoxantrone IV over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity.
|
Drug: Cytarabine
Given IV
Other Names:
Drug: Cytarabine Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos
Drug: Mitoxantrone Given IV
Other Names:
Drug: Mitoxantrone Hydrochloride Given IV
Other Names:
Drug: Peposertib Given PO
Other Names:
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients with R/R AML, defined as:
Exclusion Criteria:
Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5 and CYP2C19. Concomitant use of CYP3A4/5 substrates with a narrow therapeutic index are also excluded. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated:
Patients must not have known significant cardiopulmonary disease defined as:
United States, California | |
City of Hope Comprehensive Cancer Center | Recruiting |
Duarte, California, United States, 91010 | |
Contact: Site Public Contact 800-826-4673 becomingapatient@coh.org | |
Principal Investigator: Amandeep Salhotra | |
Los Angeles County-USC Medical Center | Recruiting |
Los Angeles, California, United States, 90033 | |
Contact: Site Public Contact 323-865-0451 | |
Principal Investigator: George Yaghmour | |
USC / Norris Comprehensive Cancer Center | Recruiting |
Los Angeles, California, United States, 90033 | |
Contact: Site Public Contact 323-865-0451 | |
Principal Investigator: George Yaghmour | |
USC Norris Oncology/Hematology-Newport Beach | Recruiting |
Newport Beach, California, United States, 92663 | |
Contact: Site Public Contact 323-865-0451 | |
Principal Investigator: George Yaghmour | |
University of California Davis Comprehensive Cancer Center | Recruiting |
Sacramento, California, United States, 95817 | |
Contact: Site Public Contact 916-734-3089 | |
Principal Investigator: Brian A. Jonas |
Principal Investigator: | Brian A Jonas | City of Hope Comprehensive Cancer Center LAO |
Tracking Information | |||||||
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First Submitted Date ICMJE | June 10, 2019 | ||||||
First Posted Date ICMJE | June 12, 2019 | ||||||
Last Update Posted Date | May 17, 2021 | ||||||
Actual Study Start Date ICMJE | October 4, 2019 | ||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Incidence of adverse events [ Time Frame: Up to 2 years ] Coded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Testing the Addition of an Anti-cancer Drug, M3814, to the Usual Treatment (Mitoxantrone, Etoposide, and Cytarabine) for Relapsed or Refractory Acute Myeloid Leukemia | ||||||
Official Title ICMJE | A Phase 1 Study of M3814 in Combination With MEC in Patients With Relapsed or Refractory Acute Myeloid Leukemia | ||||||
Brief Summary | This phase I trial studies the best dose and side effects of M3814 when given in combination with mitoxantrone, etoposide, and cytarabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). M3814 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving M3814 in combination with mitoxantrone, etoposide, and cytarabine may lower the chance of the acute myeloid leukemia growing or spreading. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: I. To assess the safety and tolerability and determine the recommended phase two dose (RP2D) of M3814 in combination with mitoxantrone, etoposide, and cytarabine (MEC) in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). SECONDARY OBJECTIVES: I. To characterize the pharmacokinetic (PK) profile of MEC alone and of M3814 in combination with MEC. II. To evaluate the preliminary efficacy of M3814 in combination with MEC in patients with R/R AML as measured by the response rate (complete remission [CR] plus CR with incomplete count recovery), duration of CR/CRi (DOR), event-free survival (EFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. To evaluate correlative biomarkers of M3814 target engagement and response. II. To correlate cytogenetic and molecular abnormalities with response. III. To evaluate the rates of early mortality and allogeneic hematopoietic cell transplantation. IV. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, whole exome sequencing (WES) and messenger ribonucleic acid (RNA) sequencing (RNAseq), in order to: IVa. Identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned. IVb. Identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and RNA-based assessment platforms. V. To contribute genetic analysis data from de-identified biospecimens to Genomic Data Commons (GDC), a well annotated cancer molecular and clinical data repository, for current and future research; specimens will be annotated with key clinical data, including presentation, diagnosis, staging, summary treatment, and if possible, outcome. OUTLINE: This is a dose-escalation study of M3814. Patients receive M3814 orally (PO) twice daily (BID) on days 2-21, mitoxantrone intravenously (IV) over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, then every 6 months thereafter. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (M3814, mitoxantrone, etoposide, cytarabine)
Patients receive M3814 PO BID on days 2-21, mitoxantrone IV over 15 minutes, etoposide IV over 60 minutes and cytarabine IV over 60 minutes on days 1-5 in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
48 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | December 31, 2021 | ||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03983824 | ||||||
Other Study ID Numbers ICMJE | NCI-2019-03607 NCI-2019-03607 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) PHI-103 10273 ( Other Identifier: City of Hope Comprehensive Cancer Center LAO ) 10273 ( Other Identifier: CTEP ) UM1CA186717 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | National Cancer Institute (NCI) | ||||||
Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | May 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |