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

NCT ID: NCT03187756

Last Updated: 2020-03-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-02
• Study Completion Date: 2018-12-18

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).

Conditions

Hematopoietic Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

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

Interventions

Cyclophosphamide

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

Intervention Type: DRUG

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-DQB1. 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.
• ECOG performance status < 2 or Karnofsky or Lansky score > 60.
• Age > 18 years and older.
• Not pregnant or breast-feeding.
• No uncontrolled infection.

Eligible diagnoses:

• Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia [CMML] with at least one of the following poor-risk features
• SLL or CLL with 17p deletion, or with progression < 6 months after second or greater treatment regimen. Must have the following to be an acceptable candidate as well:

• < 20% of bone marrow cellularity involved by SLL/CLL (to lower risk of graft rejection)
• No lymph nodes > 5 cm in any dimension
• No massive splenomegaly, defined as > 6 cm below the left costal margin
• T-cell PLL in PR or better prior to transplantation. Must also have < 20% of bone marrow cellularity involved by PLL (to lower risk of graft rejection).
• Interferon- or tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase
• Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)

o Intermediate-2 or High risk score by DIPSS Plus is required for a diagnosis of myelofibrosis

• Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen, based on the International Myeloma Working Group (IMWG) criteria.49
• Hematologic malignancy in complete remission with minimal residual disease (MRD) non detectable OR detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing or hematologic malignancies in partial remission

Donor eligibility

• Donors must be either:
• HLA-haploidentical or HLA-identical relatives of the patient based on allele or allele group level typing as defined in Section 4.1.
• Medically fit to and willing to donate
• Lack of recipient anti-donor HLA antibody
• Has not donated blood products to patient

Exclusion Criteria

• Any individual that does not meet the eligibility criteria for transplantation or donor eligibility will not be a part of this trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samer Al-Homsi, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

New York University School of Medicine

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

17-00042

Identifier Type: -

Identifier Source: org_study_id