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

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ClinicalTrials.gov Identifier: NCT02828592
Recruitment Status : Recruiting
First Posted : July 11, 2016
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
Northside Hospital, Inc.

Tracking Information
First Submitted Date  ICMJE July 6, 2016
First Posted Date  ICMJE July 11, 2016
Last Update Posted Date November 14, 2019
Actual Study Start Date  ICMJE September 9, 2016
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2016)
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%.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02828592 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2016)
  • Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events [ Time Frame: 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 ]
  • 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 ]
  • Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Severe Aplastic Anemia
Intervention  ICMJE
  • 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 Name: 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)
Study Arms  ICMJE Experimental: Flu/Cy/TBI
Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4.
Interventions:
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Radiation: Total Body Irradiation
  • Drug: Rabbit ATG
  • Drug: Cyclophosphamide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2023
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Melhem Solh, MD 404-255-1930 msolh@bmtga.com
Contact: Stacey Brown 404-851-8238 stacey.brown@northside.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02828592
Other Study ID Numbers  ICMJE NSH 1158
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Northside Hospital, Inc.
Study Sponsor  ICMJE Northside Hospital, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Melhem Solh, MD Blood and Marrow Transplant Group of Georgia
PRS Account Northside Hospital, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP