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出境医 / 临床实验 / Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias
Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias
Study Description
Brief Summary:
The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Refractory Acute Myeloid Leukemia Refractory Acute Lymphoblastic Leukemia | Drug: Preparative regimen | Phase 3 |
Detailed Description:
The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity.
The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia.
Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen.
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 25 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia. |
| Actual Study Start Date : | October 15, 2019 |
| Estimated Primary Completion Date : | July 2022 |
| Estimated Study Completion Date : | December 2022 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: intervention/treatment
Preparative chemotherapy before allogeneic HSCT
|
Drug: Preparative regimen
Preparative chemotherapy before allogeneic HSCT
|
Outcome Measures
Primary Outcome Measures :
- cumulative incidence of neutrophil and platelets engraftment at day +30 after HSCT [ Time Frame: 30 days after HSCT ]
- Overall response rate [ Time Frame: 30 days after HSCT ]Proportion of patients with hematologic remission at time points
- Partial response rate [ Time Frame: 30 days after HSCT ]Proportion of patients with MRD negativity at time points
- Rate of toxicity stage > 3 according to CTCAE 5.0 [ Time Frame: 40 days after first drug administration ]Proportion of patients with allergic/ anaphylaxis reaction toxicity stage > 3 according to CTCAE 5.0
- cumulative incidence of transplant-related mortality [ Time Frame: 100 days after HSCT ]
Secondary Outcome Measures :
- Rate of expression of target molecule on blast cells [ Time Frame: 1 week before first drug administration ]Proportion of patients with target molecule on blast cells: CD38 and/or CD 184 and/or Bcl2
- cumulative incidence of acute GVHD grade II-IV [ Time Frame: 120 days after HSCT ]
- cumulative incidence of chronic GvHD [ Time Frame: 1 year after HSCT ]
- Rate of immune recovery at day 30 [ Time Frame: 30 ]Proportion of patients with early immune recovery: T-cell, NK- cell, B-cell >determined numbers
- overall survival [ Time Frame: 1 year after HSCT ]
- event-free survival [ Time Frame: 1 year after HSCT ]
Eligibility Criteria
| Ages Eligible for Study: | up to 25 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Ability to give informed consent (for patients > 14 years old). For subjects < 18 years old their legal guardian must give informed consent
-
Disease stage
- Acute myeloid leukemia (AML), relapsed or refractory, failure to achieve hematologic remission after at least to courses of intensive chemotherapy, including at least one course with high-dose AraC and fludarabine
- Acute lymphoblastic leukemia (ALL), relapsed or refractory, failure to achieve hematologic remission after at least two high-dose therapy blocks
- Patient eligible for current hematopoietic stem cell transplantation protocol
- The BCL-2 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD38 expression must be detected on greater than 30% of tumor cells (AML and ALL) by flow cytometry
- CD184
- Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- Patient Clinical Performance Status: Karnofsky >50% or Lansky >50%
- Patient Life Expectancy >12 weeks
- Patients who agree to long-term follow up for up to 5 years
Exclusion Criteria:
- Age >25 years
- Patients with uncontrolled infections
- Clearance of creatinine < 70 ml/min
- Cardiac ejection fraction < 40%
- Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 50% predicted; patients who are unable to perform pulmonary function tests will be excluded if the oxygen (O2) saturation is < 92% on room air
- Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) >= twice the upper limit of normal
- Karnofsky/Lansky Scale <70%
Contacts and Locations
Contacts
| Contact: Larisa Shelikhova | 84956647078 | larisa.shelikhova@fccho-moscow.ru | |
| Contact: Zhanna Shekhovtsova | 84956647078 ext 7538 | zhanna.shekhovtsova@fccho-moscow.ru |
Locations
| Russian Federation | |
| Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology | Recruiting |
| Moscow, Russian Federation, 117997 | |
| Contact: Zhanna Shekhovtsova, MD 4956647078 ext 7538 zhanna.shekhovtsova@fccho-moscow.ru | |
| Contact: Eugene Pashanov, PhD +79262205578 e.pashanov@gmail.com | |
| Principal Investigator: Michael Maschan, PhD | |
Sponsors and Collaborators
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 25, 2019 | ||||||||
| First Posted Date ICMJE | June 27, 2019 | ||||||||
| Last Update Posted Date | November 20, 2020 | ||||||||
| Actual Study Start Date ICMJE | October 15, 2019 | ||||||||
| Estimated Primary Completion Date | July 2022 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures ICMJE |
|
||||||||
| Original Primary Outcome Measures ICMJE | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
|
||||||||
| Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title ICMJE | Personalized Targeted Preparative Regimen Before T-depleted Allogeneic HSCT in Children With Chemoresistent Acute Leukemias | ||||||||
| Official Title ICMJE | A Phase I-II Pilot Clinical Trial of Safety and Efficacy of Personalized Targeted Preparative Regimen With Allogeneic TcRαβ/CD19-depleted Hematopoietic Stem Cell Transplantation and Posttransplant Donor T- Cells Infusion in Children With Chemoresistаnt Acute Leukemia. | ||||||||
| Brief Summary | The purpose of this study is to evaluate the safety and efficiency of personalized targeted therapy in combination with high-dose chemotherapy as part of a preparative regimen before T-depleted allogeneic hematopoietic stem cell transplantation in children with chemoresistant acute leukemias | ||||||||
| Detailed Description |
The outcome of hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory leukemia is poor. The incidence of relapse exceeds 50% and survival varies from 10 to 40%. Additional attempts at remission induction with various combinations of chemotherapy are unlikely to improve the outcome and will contribute to toxicity. The hypothesis of the study is that personalized targeted therapy combined with high-dose chemotherapy may improve the outcome of allogeneic HSCT in a cohort of pediatric patients with refractory leukemia. Bcl-2, CD38, CD184 were chosen as potential targets due to frequent expression in pediatric acute leukemias, availability of marketed targeted therapies venetoclax, daratumumab and prelixafor, and expected non-overlapping toxicity profile of these agents and the conditioning regimen. |
||||||||
| Study Type ICMJE | Interventional | ||||||||
| Study Phase ICMJE | Phase 3 | ||||||||
| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
| Condition ICMJE |
|
||||||||
| Intervention ICMJE | Drug: Preparative regimen
Preparative chemotherapy before allogeneic HSCT
|
||||||||
| Study Arms ICMJE | Experimental: intervention/treatment
Preparative chemotherapy before allogeneic HSCT
Intervention: Drug: Preparative regimen
|
||||||||
| Publications * | Not Provided | ||||||||
|
* 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 | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
25 | ||||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||||
| Estimated Study Completion Date ICMJE | December 2022 | ||||||||
| Estimated Primary Completion Date | July 2022 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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| Sex/Gender ICMJE |
|
||||||||
| Ages ICMJE | up to 25 Years (Child, Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
|
||||||||
| Listed Location Countries ICMJE | Russian Federation | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number ICMJE | NCT04000698 | ||||||||
| Other Study ID Numbers ICMJE | NCPHOI-2018-08 | ||||||||
| Has Data Monitoring Committee | Not Provided | ||||||||
| U.S. FDA-regulated Product |
|
||||||||
| IPD Sharing Statement ICMJE | Not Provided | ||||||||
| Responsible Party | Federal Research Institute of Pediatric Hematology, Oncology and Immunology | ||||||||
| Study Sponsor ICMJE | Federal Research Institute of Pediatric Hematology, Oncology and Immunology | ||||||||
| Collaborators ICMJE | Not Provided | ||||||||
| Investigators ICMJE | Not Provided | ||||||||
| PRS Account | Federal Research Institute of Pediatric Hematology, Oncology and Immunology | ||||||||
| Verification Date | November 2020 | ||||||||
|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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