Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia

Brief Title

Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia

Official Title

A Study of T-Cell Replete, HLA-Mismatched Haploidentical Bone Marrow Transplantation With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Lacking HLA-Matched Related Donor

Brief Summary

      Severe aplastic anemia is a rare and serious form of bone marrow failure related to an
      immune-mediated mechanism that results in severe pancytopenia and high risk for infections
      and bleeding. Patients with matched sibling donors for transplantation have a 80-90% chance
      of survival; however, a response rate with just immunosuppression for those patients lacking
      suitable HLA-matched related siblings is only 60%. With immunosuppression, only 1/3 of
      patients are cured, 1/3 are dependent on long term immunosuppression, and the other 1/3
      relapse or develop a clonal disorder. Recent studies have shown that using a haploidentical
      donor for transplantation has good response rates and significantly lower rates of acute and
      chronic GVHD.
    

Detailed Description

      Mismatched haploidentical donors will be identified for patients with severe aplastic anemia.
      These patients will undergo a preparative regimen of Fludarabine/Cyclophosphamide/TBI
      followed by haploidentical bone marrow transplantation. Post-transplant Cyclophosphamide will
      be administered on Days 3 & 4. Immunosuppression with Tacrolimus and MMF will begin on Day
      +5; MMF will be discontinued on Day +35 while Tacrolimus continues until Day +180.
      Investigators hypothesize that haploidentical transplantation with the above-mentioned
      preparative regimen will have a <30% graft failure rate. The one-sided exact Binomial test at
      5% significance level will be used to test this hypothesis. The size of 20 patients provides
      the power of 92.5% for confirming the 30-day graft failure rate <30%.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant

Secondary Outcome

 Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events

Condition

Severe Aplastic Anemia

Intervention

Fludarabine

Study Arms / Comparison Groups

 Flu/Cy/TBI

Description:  Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

20

Start Date

September 9, 2016

Completion Date

August 31, 2026

Primary Completion Date

August 31, 2025

Eligibility Criteria

        Inclusion Criteria:

          -  Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor who must have negative
             HLA cross-match in the host vs. graft direction

          -  Age <= 65 years for previously treated and <= 75 years for previously treated patients

          -  KPS >= 70%

          -  Aplastic Anemia that meets the following criteria:

        Peripheral Blood (must fulfill 2 of 3):

          -  <500 PMN/mm3

          -  <20,000 platelets

          -  absolute reticulocyte count <40,000/microL

        Bone Marrow (must be either):

          -  markedly hypocellular (<25% of normal cellularity)

          -  moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral
             blood criteria above

        Exclusion Criteria:

          -  poor cardiac function (LVEF <40%)

          -  poor pulmonary function (FEV1 & FVC <50% predicted)

          -  poor liver function (bili >= 2mg/dL)

          -  poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min)

          -  prior allogeneic transplant
      

Gender

All

Ages

1 Year - 75 Years

Accepts Healthy Volunteers

No

Contacts

Melhem Solh, MD, 404-255-1930, [email protected]

Location Countries

United States

Location Countries

United States

NCT ID

NCT02828592

Organization ID

NSH 1158

Responsible Party

Sponsor

Study Sponsor

Northside Hospital, Inc.

Study Sponsor

Melhem Solh, MD, Principal Investigator, Blood and Marrow Transplant Group of Georgia

Verification Date

October 2022