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

Primary Purpose

Chronic Granulomatous Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Sirolimus

Donor peripheral blood stem cells.

Cyclophosphamide post transplant

Total body 200cGy

Cyclophosphamide

Fludarabine

Busulfan

About this trial

This is an interventional treatment trial for Chronic Granulomatous Disease focused on measuring Chronic Granulomatous Disease, Halo-Identical Protocol, Transplant

Eligibility Criteria

2 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:
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

EXCLUSION CRITERIA:

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

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CGD Recipient

Arm Description

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Outcomes

Primary Outcome Measures

To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD

Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT02282904

First Posted

November 4, 2014

Last Updated

April 30, 2020

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT02282904

Brief Title

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

Official Title

Haploidentical Transplant for Patients With Chronic Granulomatous Disease (CGD) Using Post-Transplant Cyclophosphamide

Study Type

Interventional

2. Study Status

Record Verification Date

December 10, 2019

Overall Recruitment Status

Terminated

Study Start Date

October 23, 2014 (undefined)

Primary Completion Date

April 10, 2019 (Actual)

Study Completion Date

December 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Background: - 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. Objective: - To learn the effectiveness of using cyclophosphamide with a transplant from a partially matched donor in treating CGD. Eligibility: - 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. Design: 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Granulomatous Disease

Keywords

Chronic Granulomatous Disease, Halo-Identical Protocol, Transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CGD Recipient

Arm Type

Experimental

Arm Description

CGD patients that will undergo haplo transplantation with post-transplant cyclophosphamide as described

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Other Intervention Name(s)

Rapamycin

Intervention Description

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).

Intervention Type

Biological

Intervention Name(s)

Donor peripheral blood stem cells.

Intervention Description

Infuse donor graft.

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide post transplant

Other Intervention Name(s)

Cytoxan post transplant

Intervention Description

50 mg/kg/d IV infused over 90 minutes. Day +3 and +4

Intervention Type

Radiation

Intervention Name(s)

Total body 200cGy

Intervention Description

Day -1

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

14.5 mg/kg IV over one hour Day -6 and -5

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fludara

Intervention Description

30 mg/m2 over 30 minutes Day -6 through Day -2

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

Busulfex

Intervention Description

Busulfan 3.2 mg/kg IV once daily over 2-3 hours Day -4,-3,-2

Primary Outcome Measure Information:

Title

To Determine the Efficacy of This Allogeneic Transplant Approach in Reconstituting Normal Hematopoiesis and Reversing the Clinical Phenotype of CGD

Description

Patient will have donor chimerism of greater than 20% and resolution of infection or autoimmunity at end of follow up

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Description

Time Frame

1 year post transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

2 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: Major anticipated illness or organ failure incompatible with survival from Allo-transplant Inadequate collection from prospective donors.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elizabeth M Kang, M.D.

Organizational Affiliation

National Institute of Allergy and Infectious Diseases (NIAID)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

18489989

Citation

Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolanos-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.

Results Reference

background

PubMed Identifier

21921045

Citation

Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011 Dec 1;118(23):6006-17. doi: 10.1182/blood-2011-07-338822. Epub 2011 Sep 14.

Results Reference

background

PubMed Identifier

22053277

Citation

Munchel A, Kesserwan C, Symons HJ, Luznik L, Kasamon YL, Jones RJ, Fuchs EJ. Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide. Pediatr Rep. 2011 Jun 22;3 Suppl 2(Suppl 2):e15. doi: 10.4081/pr.2011.s2.e15.

Results Reference

background

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

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