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Shortened duration immunosuppression following nonmyeloablative peripheral blood stem cell transplant with high dose post transplantation cyclophosphamide in malignancies to engraft.

Samer Al-Homsi, MD

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).

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).

Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft

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

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

Acute GVHD is graded by standard criteria, and all suspected cases of acute GVHD will be confirmed histologically by biopsy of an affected organ. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I is characterized as mild disease (skin involvement alone), Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening. The diagnosis of a chronic GVHD per NIH criteria requires a) at least 1 diagnostic manifestation or b) 1 distinctive manifestation confirmed by biopsy or testing of the same or other involved organ.

Summarize major toxicities and complications associated with the transplantation procedure

Estimate the cumulative incidence of systemic steroid initiation, by 1 year after HSCT. This is will be reported as number of participants who started steroids over the course of the study.

Graft failure and death, or graft failure, death and treatment of relapse/progressions. This will be reported as the number of participants with graft failures.

Neutrophil recovery is defined as post-nadir ANC greater than or equal to 500/mm3 for three consecutive measurements on different days. The first of the three days will be designated as the day of neutrophil recovery.

Platelet recovery is defined as sustained platelet count greater than or equal to 20,000/mm3 or greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days. The first of three consecutive measurements on different days will be designated as the day of initial platelet recovery.

NYU Langone Health

All adverse events occurring during the study period were reported. The clinical course of each event was followed up until resolution, stabilization, or until it was determined that the study treatment or participation was not the cause.

Cy 50 mg/kg IV, over approximately 1-2 hours (depending on volume), is given on Day 3 posttransplantation (ideally between 60 and 72 hours after marrow infusion) and on Day 4 (approximately 24 hours after Day 3 Cy).

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

6 participants enrolled, but only 2 participants completed

David Kaminetzky, MD

2 participants reached the 1 year time point but disease assessment was completed for only 1 subject (complete remission).

Event Free Survival (EFS)

chronic GVHD

acute grade IV GVHD

acute grade III GVHD

acute grade II GVHD

acute grade I GVHD

Number of Participants With Chronic GVHD and Grades I-IV GVHD

While AE data was reported (see AE / SAE section), due to termination of the study, relationship of major AEs to transplant procedures was unable to be assessed. Therefore, this information cannot be reported.

Spots Global Cancer Trial Database for nonmyeloablative peripheral blood stem cell transplant