Reduced-Intensity Conditioning (RIC) and Myeloablative Conditioning (MAC) for HSCT in AML/MDS

Phase 2

Completed

Conditions: Acute Myeloid Leukemia (AML)
Hematopoietic Stem Cell Transplant (HSCT)
Myelodysplastic Syndrome (MDS)

Interventions: Drug: Reduced-Intensity Conditioning Regimen
Drug: Myeloablative Conditioning Regimen

Registration Number: NCT02626715

Lead Sponsor: Randy Windreich

Brief Summary: The purpose of this study is to compare safety and efficacy of reduced-intensity conditioning and myeloablative conditioning regimens prior to HSCT in high-risk AML/MDS pediatric and young adult patients. This study investigates the use of two novel conditioning therapies for hematopoietic stem cell transplant (HSCT). The primary focus of both the investigators' myeloablative and reduced-intensity conditioning regimens is to reduce overall toxicity so that pediatric and young adult patients with high-risk AML/MDS with significant pretransplant comorbidities who would have been ineligible to proceed to HSCT previously can now receive potentially life-saving treatment.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Reduced-Intensity Conditioning	Reduced-Intensity Conditioning Regimen	Campath (alemtuzumab), Droxia (hydroxyurea), Fludara (fludarabine), Alkeran (melphalan), Thiotepa (triethylenethiophosphoramide) Trade Name (generic name)
Myeloablative Conditioning	Myeloablative Conditioning Regimen	Campath (alemtuzumab), Thiotepa (triethylenethiophosphoramide) , Fludara (fludarabine), Busulfex (busulfan) Trade Name (generic name)

Primary Outcome Measures

Name	Time	Method
Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.	Day 100	Number of non-relapsed deaths that occur
Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.	Day 180	Number of non-relapsed deaths that occur
Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.	6 months	Event-free survival at 6 months, where events are defined as relapse or death

Secondary Outcome Measures

Name	Time	Method
The Pace of Platelet Recovery	Day of transplant to end of study (Day 365)	Platelet Engraftment (the first of three consecutive days in which the platelet count exceeded 20,000/mm3 without platelet transfusions for the preceding 7 days)
Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade	Day of transplant to end of study (Day 365)	Limited cGVHD: localized skin involvement and/or hepatic dysfunction due to cGVHD. Extensive cGVHD: one or more of the following: generalized skin involvement; liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis; involvement of eye, minor salivary glands or oral mucosa based on biopsy, or any other target organ. Mild cGVHD: 1 or 2 organs involved with no more than score 1 plus lung score 0. Moderate cGVHD: 3 or more organs involved with no more than score 1, or at least one organ (not lung) with score 2, or lung score 1. Severe cGVHD: at least one organ with score 3, or lung score 2 or 3.
Day 0 Campath (Alemtuzumab) Level	Day 0	Campath (Alemtuzumab) level measured on the day of transplant
The Number of Subjects With Overall Survival (OS)	Day 100 and 180 post-transplant	The number of subjects who are alive
Pace of Immune Reconstitution	Day 180	Immune recovery as measured by lymphocyte subsets
The Pace of Neutrophil Recovery	Day of transplant to end of study (Day 365)	Neutrophil Engraftment (the first of three consecutive days in which the absolute neutrophil count (ANC) exceeded 500/mcL)
Incidence of Primary Graft Failure.	Post-transplant to 42 days post-transplant	The failure to achieve an ANC ≥500/μL after 42 days, determined by three consecutive measurements on different days, and not caused by recurrent leukemia.
Incidence of Grades 4 and 5 Adverse Events	Day 180	Adverse events as assessed by CTCAE
Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade	Day of transplant to end of study (Day 365)	Grade 0: no stage 1-4 of any organ. Grade I: stage 1-2 skin rash (stage 1: \<25%, stage 2: 25-50% body surface area affected by maculopapular rash), no gut or liver involvement. Grade II: stage 3 skin rash (\>50% body surface area affected), or stage 1 GI involvement (10-19.9 mL/kg/day volume of diarrhea), or stage 1 liver involvement (2-3 mg/dL total bilirubin level). Grade III: stage 0-3 skin rash with stage 2-4 GI involvement (stage 2: 20-30 mL/kg/day, stage 3: \>30 mL/kg/day volume of diarrhea, stage 4: severe abdominal pain with or without ileus and/or grossly blood stool) or stage 2-3 liver involvement (stage 2: 3-6 mg/dL, stage 3: 6-15 mg/dL total bilirubin level). Grade IV: stage 4 skin rash (generalized erythroderma with bullous formation) or stage 4 liver involvement (\>15 mg/dL total bilirubin level).
Disease-free Survival (DFS)	Day 100 and 180 post-transplant	The number of subjects who are alive without relapse/leukemia
Treatment-related Mortality (TRM)	Day 100 and 180 post-transplant	The number of subjects deceased due to transplant-related (i.e. non-relapse) causes