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

April 15, 2026 updated by: Northside Hospital, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Northside Hospital
        • Contact:
        • Sub-Investigator:
          • Asad Bashey, MD, PhD
        • Sub-Investigator:
          • Lawrence Morris, MD
        • Sub-Investigator:
          • Scott Solomon, MD
        • Contact:
        • Principal Investigator:
          • Melhem Solh, MD
        • Sub-Investigator:
          • H. Kent Holland, MD
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Blood and Marrow Transplant Group of Georgia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant
Time Frame: 2 years
Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be <30%.
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events
Time Frame: 2 years
2 years
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
Time Frame: 2 years
2 years
Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course
Time Frame: 2 years
2 years
Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northside Hospital, Inc.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 9, 2016

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2028

Study Registration Dates

First Submitted

July 6, 2016

First Submitted That Met QC Criteria

July 6, 2016

First Posted (Estimated)

July 11, 2016

Study Record Updates

Last Update Posted (Actual)

April 20, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSH 1158

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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