Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) Initial Salvage Therapy for Induction Failure Acute Myeloid Leukemia (AML)
2 other identifiers
interventional
11
1 country
1
Brief Summary
Objectives: Primary Objectives:
- 1.To determine the safety and feasibility of allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage treatment for patients with primary induction failure (PIF) acute myeloid leukemia (AML).
- 2.To determine efficacy of AHSCT following decitabine, clofarabine, idarubicin, and cytarabine (DCIA) salvage chemotherapy evaluated by overall response rate (RR), defined as complete response (CR) or CR without platelet recovery (CRp) or CR with insufficient hematological recovery (CRi).
- 3.To determine the percentage of patients with PIF AML eligible for AHSCT after up to 2 courses of induction chemotherapy.
- 4.To determine the early treatment-related mortality (TRM) (within first 4 weeks of first salvage chemotherapy regimen with DCIA and day 100 TRM after AHSCT.
- 5.To determine the efficacy DCIA regimen as salvage chemotherapy for patients with PIF AML (% of patients who achieve \</=5% bone marrow blasts prior to AHSCT.
- 6.To determine the TRM at 1 year, relapse rate (RR), overall survival (OS) and event-free survival (EFS) for patients with PIF AML treated with DCIA followed by early AHSCT.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 leukemia
Started Sep 2015
Typical duration for phase_2 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2015
CompletedFirst Posted
Study publicly available on registry
May 12, 2015
CompletedStudy Start
First participant enrolled
September 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 22, 2021
CompletedResults Posted
Study results publicly available
January 17, 2024
CompletedFebruary 22, 2024
February 1, 2024
5 years
May 5, 2015
November 7, 2023
February 20, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Response (OR) Post Transplant
Number of participants classified as achieving overall response of complete remission(CR: \< 5% blast in a bone marrow/and platelet \>100/and ANC \>1) or CR without platelet recovery (CRp: \< 5% blast in a bone marrow/and platelet \<100/and ANC \>1) or CR with insufficient hematological recovery (CRi: \< 5% blast in a bone marrow/and platelet \>100/and ANC \<1) post transplant.
4 months after initial treatment/3 months after transplant
Treatment-Related Mortality (TRM)
Number of participants died from treatment-related death within 4 months post initial treatment/3 months post transplant.
4 months post initial treatment/3 months post transplant
Secondary Outcomes (1)
Overall Survival (OS)
1 year
Study Arms (3)
Matched Sibling Donor Group
EXPERIMENTALSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Stem cell infusion performed on Day 0.
Haploidentical Donor Group
EXPERIMENTALSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Total body irradiation (TBI) delivered at 2Gy on Day -2. Stem cell infusion performed on Day 0. Cyclophosphamide 50 mg/kg by vein on Days +3 and +4. Tacrolimus 0.015 mg/kg/day by vein or mouth on Day +5. Mycophenolate mofetil 15 mg/kg/dose by vein or by mouth three times a day from Day +5 to Day+100.
Matched Unrelated Donor Group
EXPERIMENTALSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Thymoglobulin 2.0 mg/Kg by vein on Days -3 and -2. Stem cell infusion performed on Day 0.
Interventions
Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3.
Fludarabine 10 mg/m2 by vein on Days -6 to -3.
Salvage Chemotherapy Before Transplant: Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Clofarabine 40 mg/m2 by vein on Days -6 to -3.
Total body irradiation (TBI) delivered at 2Gy on Day -2.
Thymoglobulin 2.0 mg/Kg by vein on Days -3 and -2.
Fresh or cryopreserved bone marrow or peripheral blood (PB) progenitor cells infused on Day 0. Goal is to infuse 4 X 106 CD34+ cells/kg if PB or \>3.0 X 108 marrow mononuclear cells/kg if bone marrow.
Cyclophosphamide 50 mg/kg by vein on Days +3 and +4.
Tacrolimus 0.015 mg/kg/day by vein or mouth on Day +5.
Mycophenolate mofetil 15 mg/kg/dose by vein or by mouth three times a day from Day +5 to Day+100.
20 mg/m2 by vein on Days 1 - 5.
1 g/m2 by vein on Days 6 - 10.
10 mg/m2 by vein on Days 6 - 8.
Eligibility Criteria
You may qualify if:
- Patients age 18-60 years.
- Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML induction therapy (\> 5% blasts on day 21 (+/-7 days) bone marrow aspirate and/or biopsy from the beginning of induction chemotherapy, up to 42 days).
- Eastern Cooperative Oncology Group (ECOG) Performance Status \</= 2.
- Adequate major organ function:, defined as: a) Serum creatinine \</= 3 mg/dL; b) Total bilirubin \</= 2.5 mg/dL; c) ALT (SGPT) \</= 3 x ULN or \</= 5 x ULN if related to disease; d) Cardiac ejection fraction \>/= 40% (by either ECHO or MUGA).
- Willingness to have an allogeneic transplant.
- Patient or patient's legal representative able to provide written informed consent.
- Patients are required to meet the following criteria to proceed to AHSCT:
- Donor criteria: Availability of a donor either an HLA matched sibling donor (MSD) or a haploidentical (5-9/10 HLA matched); alternatively a 8/8 HLA matched unrelated donor (MUD) by high resolution typing is immediately available;
- Disease criteria: Day 21 (+/-7 days) bone marrow aspiration or biopsy from the beginning of salvage DCIA: a. In complete morphologic remission with \<5% bone marrow blasts, or b. Aplastic (\<10% bone marrow cellularity), and cytopenic with an absolute neutrophil count (ANC) less than 1,000/µL, or c. Low disease burden with \< 30% BM blasts, with recovery of peripheral blood (PB) WBC (ANC\>1,000/µL) and \<5% circulating blasts.
- Adequate organ function criteria: a. Serum creatinine clearance \>/= 50 ml/min (calculated by Cockcroft-Gault formula); b. Total bilirubin \</= 2 times upper limit of normal (x ULN) (3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); c. Alanine aminotransferase (ALT) \</= 3 x ULN (5.0 x ULN if considered to be due to leukemic involvement); d. LVEF \>/= 40% on ECHO or MUGA; e. DLCO \>/= 50% predicted after correction for hemoglobin (must be performed in patients with history of smoking or lung disease;); DLCO may be omitted in patients without history of pulmonary disease if approved by the Study Chair.
- No active infection: Patients should be afebrile. If present, pulmonary infiltrates or other sites of infection must be improving on antibiotics. Patients should not require oxygen. Study Chair will be the arbiter of this criterion.
You may not qualify if:
- HIV positive; active hepatitis B or C.
- Uncontrolled active infections (viral, bacterial, and fungal); the Study Chair will be the final arbiter of this criterion.
- Patients with active secondary malignancy unless approved by the Study Chair.
- Liver cirrhosis.
- Active CNS involvement within the previous 2 months.
- Prior induction therapy with DAC + CIA.
- Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- Breast feeding women.
- Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
- Inability to comply with medical therapy or follow-up.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Richard Champlin, MD/Stem Cell Transplantation
- Organization
- University of Texas MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Stefan Ciurea, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 5, 2015
First Posted
May 12, 2015
Study Start
September 14, 2015
Primary Completion
September 22, 2020
Study Completion
September 22, 2021
Last Updated
February 22, 2024
Results First Posted
January 17, 2024
Record last verified: 2024-02