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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 : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
Northside Hospital, Inc.

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
Severe Aplastic Anemia Drug: Fludarabine Drug: Cyclophosphamide Radiation: Total Body Irradiation Drug: Rabbit ATG 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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
Study Start Date : September 2016
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : September 2022


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 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)




Primary Outcome Measures :
  1. 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%.


Secondary Outcome Measures :
  1. Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 2 years ]
  4. Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points [ Time Frame: 2 years ]


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Ages Eligible for Study:   1 Year to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02828592


Contacts
Contact: Melhem Solh, MD 404-255-1930 msolh@bmtga.com
Contact: Stacey Brown 404-851-8238 stacey.brown@northside.com

Locations
United States, Georgia
Blood and Marrow Transplant Group of Georgia Recruiting
Atlanta, Georgia, United States, 30342
Contact: Melhem Solh, MD    404-255-1930    msolh@bmtga.com   
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Melhem Solh, MD    404-255-1930    msolh@bmtga.com   
Contact: Stacey Brown    404-851-8238    stacey.brown@northside.com   
Sub-Investigator: Scott Solomon, MD         
Sub-Investigator: H. Kent Holland, MD         
Sub-Investigator: Asad Bashey, MD, PhD         
Sub-Investigator: Lawrence Morris, MD         
Principal Investigator: Melhem Solh, MD         
Sponsors and Collaborators
Northside Hospital, Inc.
Investigators
Principal Investigator: Melhem Solh, MD Blood and Marrow Transplant Group of Georgia

Publications of Results:

Other Publications:
Responsible Party: Northside Hospital, Inc.
ClinicalTrials.gov Identifier: NCT02828592     History of Changes
Other Study ID Numbers: NSH 1158
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Northside Hospital, Inc.:
SAA

Additional relevant MeSH terms:
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Cyclophosphamide
Fludarabine phosphate
Thymoglobulin
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites