Phase II Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft
Overview
- Phase
- Phase 2
- Intervention
- Cyclophosphamide
- Conditions
- Hematopoietic Malignancies
- Sponsor
- NYU Langone Health
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Event Free Survival (EFS)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
This is an open label phase II single arm study of peripheral blood stem cell transplantation and posttransplantation cyclophosphamide, using HLA full match or haploidentical related donors, in hematological malignancies including those difficult to engraft. The objective of this study is to evaluate the safety and feasibility in nonmyeloablative, partially HLA-mismatched or HLA-matched PBSC transplant from haploidentical donors or fully matched donors with post-grafting immunosuppression that includes high-dose cyclophosphamide, tacrolimus, and Mycophenolate mofetil (MMF).
Detailed Description
Primary Objective Estimate event free survival (EFS) (relapse, progression, or death) rate one year after transplant. Secondary Objectives: 1. Estimate the cumulative incidences of severe acute grade III or higher GVHD, chronic GVHD (overall and by extent) 2. Estimate the cumulative incidence of systemic steroid initiation, 3. Summarize the graft failure frequency, 4. Summarize the kinetics of neutrophil and platelet recovery, and kinetics of donor chimerism in unsorted and CD3+ sorted peripheral blood. 5. Summarize major toxicities and complications associated with the transplantation procedure selected toxicities. Exploratory Objectives: Explore the association between the amount of donor T cell chimerism at \~ Day 28 and patient/graft characteristics (e.g., prior therapies, graft cell dose) and transplantation outcomes (sustained engraftment, relapse or progression, GVHD).
Investigators
Eligibility Criteria
Inclusion Criteria
- •The following are eligibility for study entry and transplantation.
- •Presence of a suitable related, HLA-haploidentical or HLA-matched stem cell donor
- •The donor and recipient must be identical at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB
- •A minimum match of 5/10 is therefore required for related donors, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
- •Eligible diagnoses:
- •Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia \[CMML\] with at least one poor risk factor
- •No active extramedullary leukemia or known active CNS involvement by malignancy. Such disease treated into remission is permitted.
- •Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning
- •No previous allogeneic HSCT
- •Adequate end-organ function Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
Exclusion Criteria
- •Any individual that does not meet the eligibility criteria for transplantation or donor eligibility will not be a part of this trial.
Arms & Interventions
Cyclophosphamide
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Event Free Survival (EFS)
Time Frame: One Year
Estimate the one year after transplantation event free survival (EFS) rate using a Kaplan-Meier curve with a 90% confidence interval. An event for EFS is defined as the first of any of the following failures: relapse or disease progression or death from any cause
Secondary Outcomes
- Number of Participants With Chronic GVHD and Grades I-IV GVHD(1 year)
- Number of Major Toxicities and Complications Associated With Transplantation Procedure(1 year)
- Cumulative Incidences of Systemic Steroid Initiation(1 year)
- Graft Failure Frequency(1 year)
- Time to Neutrophil Recovery(1 year)
- Time to Platelet Recovery(1 year)