Venetoclax-containing Therapy Combined With Microtransplant for Newly Diagnosed AML
Not Applicable
Recruiting
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Drug: Idarubicin（IDA）Biological: GPBMC infusion
- Registration Number
- NCT07078591
- Lead Sponsor
- Beijing 302 Hospital
- Brief Summary
The purpose of this study is to evaluate whether HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion with venetoclax-containing regimens (microtransplant, MST) could improve survival in adult patients with newly diagnosed acute myeloid leukemia (AML).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Inclusion Criteria
- Age >=18 years, male or female, non-limited by race or ethnicity.
- No prior anti-acute leukemia treatment (including hypomethylators for leukemia or MDS) with the exception that prior hydroxyurea and/or leukapheresis are permitted.
- Confirmed acute myeloid leukemia in accordance with WHO criteria with a WBC count < 25 × 109/L.
- Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )<= 3 × upper limit of normal(ULN), and total bilirubin <= 1.5 × ULN.
- Adequate renal function including serum creatinine <= 2 × ULN or CrCl>= 40mL/min.
- LVEF measured by echocardiogram is within the normal range (LVEF > 50%).
- The subject must have one donor who is >= 18 years old and HLA matched at 0-7/10 loci (i.e., at least 3 HLA loci must be mismatched). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form.
- Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research.
- Donor inclusion criteria: The donor meets the institution's criteria for related peripheral blood hematopoietic stem cell donors. The donor must be able to tolerate the cell separation and collection process, and sign the Informed Consent Form.
Exclusion Criteria
- Acute promyelocytic leukemia, myeloid sarcoma, chronic myeloid leukemia accelerated phase and blast crisis.
- Uncontrolled infection or hemorrhage.
- Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
- Uncontrolled autoimmune disease or requiring immunosuppression treatment.
- History of severe blood infusion reaction.
- Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
- Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements.
- Any major surgery within 4 weeks before enrollment.
- Life-threatening illness other than AML or uncontrolled intercurrent illness.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1 Venetoclax This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 1 Azacitidine (AZA) This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 1 Daunorubicin This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 1 Idarubicin（IDA） This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 1 Cytarabine (Ara-C) This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 1 GPBMC infusion This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Cohort 2 Venetoclax This cohort will include patients unfit for intensive therapy but fit for lower intensity therapy at diagnosis according to Ferrara 2013 criteria. Induction phase: Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Re-evaluate unfitness and continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Convert to "fit" patients and \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Convert to "fit" patients and ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Still "unfit" patients Venetoclax 400 mg on Days 1-14 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. Infuse donor GPBMCs on Day 15. 28 days per cycle until progression or untolerated. Cohort 2 Azacitidine (AZA) This cohort will include patients unfit for intensive therapy but fit for lower intensity therapy at diagnosis according to Ferrara 2013 criteria. Induction phase: Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Re-evaluate unfitness and continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Convert to "fit" patients and \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Convert to "fit" patients and ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Still "unfit" patients Venetoclax 400 mg on Days 1-14 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. Infuse donor GPBMCs on Day 15. 28 days per cycle until progression or untolerated. Cohort 2 Cytarabine (Ara-C) This cohort will include patients unfit for intensive therapy but fit for lower intensity therapy at diagnosis according to Ferrara 2013 criteria. Induction phase: Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Re-evaluate unfitness and continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Convert to "fit" patients and \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Convert to "fit" patients and ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Still "unfit" patients Venetoclax 400 mg on Days 1-14 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. Infuse donor GPBMCs on Day 15. 28 days per cycle until progression or untolerated. Cohort 2 GPBMC infusion This cohort will include patients unfit for intensive therapy but fit for lower intensity therapy at diagnosis according to Ferrara 2013 criteria. Induction phase: Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Re-evaluate unfitness and continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Convert to "fit" patients and \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Convert to "fit" patients and ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Still "unfit" patients Venetoclax 400 mg on Days 1-14 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. Infuse donor GPBMCs on Day 15. 28 days per cycle until progression or untolerated.
- Primary Outcome Measures
Name Time Method Overall survival (OS) Measured up to 4 years after the last participant is enrolled OS is defined as the number of days from the date of initiation of treatment to the date of death.
Event-free Survival (EFS) Measured up to 4 years after the last participant is enrolled EFS is defined as the number of days from initiation of treatment to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.
- Secondary Outcome Measures
Name Time Method Complete remission (CR) and complete remission with incomplete marrow recovery (CRi) Measured up to 2 years after the last participant is enrolled CR is defined as absolute neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, red cell transfusion independence, and bone marrow with \< 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophil count \<= 1 × 109/L or platelet count \<= 100 × 109/L.
Partial remission (PR) Measured up to 2 years after the last participant is enrolled PR is defined as decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow, peripheral blood neutrophil count \> 1 × 109/L, platelet count \> 100 × 109/L, red cell transfusion independence.
Non-relapse Mortality (NRM) Measured up to 4 years after the last participant is enrolled NRM is defined as the death without relapse.
Trial Locations
- Locations (1)
Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
🇨🇳Beijing, China
Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital🇨🇳Beijing, ChinaBo Cai, MDPrincipal InvestigatorYangyang Lei, MDContact+861066947180942056176@qq.com