Post-transplant Cyclophosphamide for Acute Myeloid Leukemia

Phase-Based Progress Estimates
1
Effectiveness
2
Safety
Acute Myeloid Leukemia+7 MorePost-transplant Cyclophosphamide - Drug
Eligibility
Any Age
All Sexes
What conditions do you have?
Select

Study Summary

This trial will study the use of HCT with MMUD in patients with hematologic malignancies, using PTCy, tacrolimus, and MMF for GVHD prophylaxis.

Eligible Conditions
  • Mixed Phenotype Acute Leukemia
  • Chronic Lymphocytic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Leukemia
  • Lymphoma
  • Myelodysplastic Syndrome
  • Leukemia

Treatment Effectiveness

Study Objectives

1 Primary · 20 Secondary · Reporting Duration: 1 year post-HCT

1 year post HCT
Overall Survival
1 year post-HCT
Cumulative incidence of chronic GVHD
Cumulative incidence of relapse/progression
Cumulative incidence of secondary graft failure
Event-Free Survival based on donor HLA match grade and donor age (7/8 versus <7/8)
Event-free survival
GVHD, relapse free survival
Modified GVHD, relapse free survival
Overall Survival based on donor HLA match grade and donor age (7/8 versus <7/8)
Overall Toxicity
Progression-free survival
Year 1
Perinatal death
Day +100 post-HCT
Cumulative incidence of acute GVHD
Cumulative incidence of neutrophil recovery
Cumulative incidence of platelet recovery
Donor chimerism
Kinetics of neutrophil recovery
Blood Platelets
Day +14 post-HCT
Craniosynostosis
Day +28 post-HCT
Cumulative incidence of primary graft failure
Days +100 and +180 post-HCT
Cytomegalovirus Infections

Trial Safety

Safety Progress

2 of 3
This is further along than 68% of similar trials

Trial Design

7 Treatment Groups

Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)
1 of 7
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)
1 of 7
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)
1 of 7
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)
1 of 7
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)
1 of 7
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)
1 of 7
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)
1 of 7

Experimental Treatment

300 Total Participants · 7 Treatment Groups

Primary Treatment: Post-transplant Cyclophosphamide · No Placebo Group · Phase 2

Regimen E (NMA: Fludarabine, Cyclophosphamide, TBI; PBSC HCT)Experimental Group · 9 Interventions: Tacrolimus, Total-body irradiation, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Cyclophosphamide, Mycophenolate Mofetil, Fludarabine, PBSC Hematopoietic Stem Cell Transplantation (HSCT) · Intervention Types: Drug, Radiation, Other, Drug, Drug, Drug, Drug, Drug, Procedure
Regimen A (MAC: busulfan and fludarabine, PBSC HCT)Experimental Group · 8 Interventions: Tacrolimus, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Mycophenolate Mofetil, Fludarabine, Busulfan, PBSC Hematopoietic Stem Cell Transplantation (HSCT) · Intervention Types: Drug, Other, Drug, Drug, Drug, Drug, Drug, Procedure
Regimen B (MAC: Fludarabine and TBI; PBSC HCT)Experimental Group · 8 Interventions: Tacrolimus, Total-body irradiation, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Mycophenolate Mofetil, Fludarabine, PBSC Hematopoietic Stem Cell Transplantation (HSCT) · Intervention Types: Drug, Radiation, Other, Drug, Drug, Drug, Drug, Procedure
Regimen C (RIC: Fludarabine and Busulfan; PBSC HCT)Experimental Group · 8 Interventions: Tacrolimus, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Mycophenolate Mofetil, Fludarabine, Busulfan, PBSC Hematopoietic Stem Cell Transplantation (HSCT) · Intervention Types: Drug, Other, Drug, Drug, Drug, Drug, Drug, Procedure
Regimen D (RIC: Fludarabine and Melphalan; PBSC HCT)Experimental Group · 8 Interventions: Tacrolimus, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Mycophenolate Mofetil, Fludarabine, Melphalan, PBSC Hematopoietic Stem Cell Transplantation (HSCT) · Intervention Types: Drug, Other, Drug, Drug, Drug, Drug, Drug, Procedure
Regimen F (MAC: Busulfan and Cyclophosphamide; BM HCT)Experimental Group · 8 Interventions: Tacrolimus, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Cyclophosphamide, Mycophenolate Mofetil, Busulfan, Bone Marrow Hematopoietic Stem Cell Transplantation · Intervention Types: Drug, Other, Drug, Drug, Drug, Drug, Drug, Procedure
Regimen G (MAC: Cyclophosphamide and TBI; BM HCT)Experimental Group · 8 Interventions: Tacrolimus, Total-body irradiation, Patient-Reported Outcomes, Post-transplant Cyclophosphamide, Mesna, Cyclophosphamide, Mycophenolate Mofetil, Bone Marrow Hematopoietic Stem Cell Transplantation · Intervention Types: Drug, Radiation, Other, Drug, Drug, Drug, Drug, Procedure
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Tacrolimus
FDA approved
Coenzyme M
FDA approved
Cyclophosphamide
FDA approved
Mycophenolate mofetil
FDA approved
Fludarabine
FDA approved
Busulfan
FDA approved
Melphalan
FDA approved

Trial Logistics

Trial Timeline

Screening: ~3 weeks
Treatment: Varies
Reporting: 1 year post-hct

Who is running the clinical trial?

National Marrow Donor ProgramOTHER
59 Previous Clinical Trials
182,149 Total Patients Enrolled
Center for International Blood and Marrow Transplant ResearchLead Sponsor
34 Previous Clinical Trials
200,173,778 Total Patients Enrolled
Steven Devine, MDPrincipal InvestigatorNMDP/Be The Match
3 Previous Clinical Trials
90 Total Patients Enrolled

Eligibility Criteria

Age Any Age · All Participants · 10 Total Inclusion Criteria

Mark “Yes” if the following statements are true for you:
You are between 18 and 66 years old (for chemotherapy-based conditioning) or up to 61 years old (for total body irradiation [TBI]-based conditioning) when you signed the informed consent.
You meet the specified requirements of the study protocol for your medication regimen.
You must have at least 4 out of 8 matches for HLA-A, -B, -C and -DRB1 antigens available on your immunologic profile and be under 35 years old.
You plan to infuse PBSC.
Your HCT Comorbidity Index is less than 5.
You have been diagnosed with AML, ALL or another acute leukemia in 1st remission or beyond and must demonstrate ≤ 5% marrow blasts and no circulating blasts as evidenced by recent bone marrow assessment within 45 days prior to the start of treatment.
Your estimated creatinine clearance is more than 60 mL/min, calculated by equation.
Your most recent pulmonary function test results indicate that your diffusing capacity of the lungs for carbon monoxide (DLCO) corrected for hemoglobin and forced expiratory volume in first second (FEV1) predicted are both greater than 50%.
Your left ventricular ejection fraction is greater than 45% according to the most recent echocardiogram or MUGA results.
MDS patients with no detectable circulating blasts and bone marrow blast percentage < 10% (higher percentages allowed given lack of differences in outcomes between those with < 5% or 5-10%) must have had a documented bone marrow assessment within 45 days prior to the planned start of conditioning.