Total Marrow and Lymphoid Irradiation, Fludarabine, and Melphalan Before Donor Stem Cell Transplant in Treating Participants With High-Risk Acute Leukemia or Myelodysplastic Syndrome
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Acute Lymphoblastic Leukemia
- Acute Lymphoblastic Leukemia in Remission
- Acute Myeloid Leukemia
- Acute Myeloid Leukemia in Remission
- Hematopoietic Cell Transplantation Recipient
- Minimal Residual Disease
- Myelodysplastic Syndrome
- Secondary Acute Myeloid Leukemia
- Type
- Interventional
- Phase
- Phase 1
- Design
- Allocation: N/AIntervention Model: Single Group AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 12 years and 125 years
- Gender
- Both males and females
Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose/recommended phase II dose (MTD/RP2D) of total marrow and lymphoid irradiation (TMLI) with fixed doses of fludarabine and melphalan (FM100) as a preparative regimen in patients undergoing allogeneic hematopoietic stem cell transplantation...
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose/recommended phase II dose (MTD/RP2D) of total marrow and lymphoid irradiation (TMLI) with fixed doses of fludarabine and melphalan (FM100) as a preparative regimen in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) and who are not eligible for standard myeloablative regimens, with either a matched donor (Arm A) or a haploidentical donor (Arm B). II. To describe toxicities attributable to TMLI by dose level in patients treated under this regimen. SECONDARY OBJECTIVES: I. To evaluate the safety of the regimen, at each dose level, by assessing the following: type, frequency, severity, attribution, time course and duration of adverse events, including acute/chronic graft versus host disease (GVHD), infection and delayed engraftment. II. To investigate the temporal effect of bone marrow residual damage in alloHCT patients after TMLI/FM100. III. To estimate overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100 days, 1 year and 2 years. IV. Assess minimal residual disease (MRD) from bone marrow aspirates on days 30, 100, and 180 post-transplant and describe its relation to TMLI dose level and patient disease status. V. To evaluate effect of TMLI/FM100 conditioning on immune reconstitution after alloHCT in patients receiving stem cells from matched or haploidentical donors. OUTLINE: This is a dose-escalation study of TMLI. Participants undergo TMLI twice daily (BID) on days -8 to -5, and receive fludarabine intravenously (IV) on days -4 to -2 and melphalan on day -2. Participants then undergo alloHCT on day 0. After completion of study treatment, participants are followed up twice weekly for 100 days, twice monthly for 6 months, and then monthly or yearly for up to 2 years.
Tracking Information
- NCT #
- NCT03494569
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Principal Investigator: Monzr Al Malki City of Hope Medical Center