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Haploidentical Transplant for People With Chronic Granulomatous Disease Using Post Transplant Cyclophosphamide

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ClinicalTrials.gov Identifier: NCT02282904
Recruitment Status : Terminated
First Posted : November 5, 2014
Results First Posted : May 1, 2020
Last Update Posted : May 12, 2020
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:


- Chronic Granulomatous Disease (CGD) causes immune system problems. Treatment is usually a bone marrow transplant from a fully matched donor. Researchers want to try using partially matched donors for patients who do not have a fully matched donor available. The researchers will also use the drug cyclophosphamide to try to improve the outcomes when using a partially matched donor.


- To learn the effectiveness of using cyclophosphamide with a transplant from a partially matched donor in treating CGD.


- Recipients: age 2-65 with CGD with an ongoing infection that has not been cured by standard treatment and no fully matched donor available in an appropriate timeframe.


  • Recipients will:

    • be admitted to the hospital 2 weeks before transplant.
    • be screened with blood and urine tests, breathing and heart health tests, X-rays, and/or magnetic resonance imaging. They may have a bone marrow aspiration and biopsy.
  • meet with a social worker and dentist.
  • get chemotherapy, radiation, and other medicines.
  • get an intravenous (IV) catheter in their chest.
  • have the transplant.
  • get more medicines and standard supportive care.
  • have blood drawn frequently.
  • have to stay in the Washington, D.C. area for 3 months post-transplant.
  • be followed closely for the first 6 months, and then less frequently for at least 5 years.

Condition or disease Intervention/treatment Phase
Chronic Granulomatous Disease Drug: Sirolimus Biological: Donor peripheral blood stem cells. Drug: Cyclophosphamide post transplant Radiation: Total body 200cGy Drug: Cyclophosphamide Drug: Fludarabine Drug: Busulfan Phase 1 Phase 2

Detailed Description:
Allogeneic transplant using HLA matched donors, both related and unrelated, has proven curative for patients with various immunodeficiencies, including those with ongoing infections. However donor availability remains a limiting factor in the application of this treatment modality. The use of haploidentical donors has in the past been fraught with a greater rate of complications related to both higher rates of GvHD and delayed immunorecovery. Newer transplant regimens appear to have diminished these risks and improved outcomes. We propose using a subablative conditioning regimen followed by post-transplant cyclophosphamide for patients with CGD who do not have an HLA matched donor but whose circumstances necessitate the use of a potentially curative, albeit high-risk treatment modality.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Post-Transplant Cyclophosphamide
Study Start Date : October 23, 2014
Actual Primary Completion Date : April 10, 2019
Actual Study Completion Date : December 10, 2019

Arm Intervention/treatment
Experimental: CGD Recipient
CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described
Drug: Sirolimus

For pediatric patients: Begin sirolimus 1 mg/m2 PO q4h for 3 doses, then 1 mg/m2 once a day (QD). For adult patients, begin sirolimus 5 mg PO q4h for 3 doses, then 5 mg once a day (QD).

Doses may be adjusted to maintain trough levels between 8-14 ng/ml. Recipients will take sirolimus from Day +5 to at least Day 100 (minimum).

Other Name: Rapamycin

Biological: Donor peripheral blood stem cells.
Infuse donor graft.

Drug: Cyclophosphamide post transplant
50 mg/kg/d IV infused over 90 minutes. Day +3 and +4
Other Name: Cytoxan post transplant

Radiation: Total body 200cGy
Day -1

Drug: Cyclophosphamide
14.5 mg/kg IV over one hour Day -6 and -5
Other Name: Cytoxan

Drug: Fludarabine
30 mg/m2 over 30 minutes Day -6 through Day -2
Other Name: Fludara

Drug: Busulfan
Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2
Other Name: Busulfex

Primary Outcome Measures :
  1. To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD [ Time Frame: 5 years ]
    Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up

Secondary Outcome Measures :
  1. To Determine the Safety of This Allogeneic HSCT Approach in Patients With CGD Including Transplant Related Toxicity, the Incidence of Acute and Chronic Graft-versus-host Disease, Immune Reconstitution, Overalland Disease-free Survival. [ Time Frame: 1 year post transplant ]
    1. Stable chimerism as indicated by 30-50% myeloid engraftment and 50% lymphoid engraftment as assessed by 1 year post transplant. 2. Immune reconstitution levels with DHR as a marker of normal neutrophil function by 1 year post transplant. 3. GvHD grades of less than 3.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • Must have sufficient complications from underlying disease to warrant undergoing transplantation
  • Ages 2 years - 65 years
  • No appropriate HLA matched donor (available donor has greater than 1 mismatch or the single mismatch is not at DQ for unrelated donors (including cord blood products), or no available 6 out of 6 HLA matched related donor), or patients who may have an unrelated donor, but whose clinical status is such that the time required to obtain an unrelated donor would be life threatening.
  • HLA haploidentical family donor graft available.
  • Ability to comprehend and willingness to sign the informed consent or have a parent/guardian consent if the donor is a minor; assent being obtained from minors as appropriate
  • Must be HIV negative
  • Must not be pregnant (confirmed by a negative serum beta-human chorionic gonadotropin (Beta-hCG) for women of child-bearing potential) or breastfeeding
  • Must be able to stay within one hour s travel of the NIH for the first 3 months after transplantation and have a family member or other designated companion to stay with during the post-transplant period.
  • Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance to NIH Form-200 NIH Durable Power of Attorney for Health Care Decision Making.
  • Where appropriate, subjects must agree to use contraception for 3 months post-transplant


  • Major anticipated illness or organ failure incompatible with survival from Allo-transplant
  • Inadequate collection from prospective donors.

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): NCT02282904

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Elizabeth M Kang, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  Study Documents (Full-Text)

Documents provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Informed Consent Form  [PDF] June 18, 2018

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02282904    
Other Study ID Numbers: 150007
15-I-0007 ( Other Identifier: NIH )
First Posted: November 5, 2014    Key Record Dates
Results First Posted: May 1, 2020
Last Update Posted: May 12, 2020
Last Verified: December 10, 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Chronic Granulomatous Disease
Halo-Identical Protocol
Additional relevant MeSH terms:
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Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents