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

Sponsor
Northside Hospital, Inc. (Other)
Overall Status
Recruiting
CT.gov ID
NCT02828592
Collaborator
(none)
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2
1
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Sep 9, 2016
Anticipated Primary Completion Date :
Aug 31, 2025
Anticipated Study Completion Date :
Aug 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Flu/Cy/TBI

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

Drug: Fludarabine
30 mg/m2 IV QD x 5 days (Days -6 to -2)

Drug: Cyclophosphamide
14.5 mg/kg/day IV x 2 doses (Days -6 & -5)

Radiation: Total Body Irradiation
300 cGy x1 dose (Day -1)
Other Names:
  • TBI
  • Drug: Rabbit ATG
    1.5 mg/kg/day x 3 days (Days -3 to -1)

    Drug: Cyclophosphamide
    Post-transplant: 50 mg/kg IV QD (Day +3 to +4)

    Outcome Measures

    Primary Outcome Measures

    1. Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant [2 years]

      Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be <30%.

    Secondary Outcome Measures

    1. Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events [2 years]

    2. Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease at 100 days post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course [2 years]

    3. Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course [2 years]

    4. Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points [2 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Year to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Blood and Marrow Transplant Group of Georgia Atlanta Georgia United States 30342
    2 Northside Hospital Atlanta Georgia United States 30342

    Sponsors and Collaborators

    • Northside Hospital, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Northside Hospital, Inc.
    ClinicalTrials.gov Identifier:
    NCT02828592
    Other Study ID Numbers:
    • NSH 1158
    First Posted:
    Jul 11, 2016
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Northside Hospital, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 5, 2022