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

NCT02282904 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 15000715-I-0007
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Granulomatous Disease

Keywords

Chronic Granulomatous Disease; Halo-Identical Protocol; Transplant

Outcome Measures

Primary Outcomes (1)

• 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

  5 years

Secondary Outcomes (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.

  1 year post transplant

Study Arms (1)

CGD Recipient

EXPERIMENTAL

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

Drug: Sirolimus; Biological: Donor peripheral blood stem cells.; Drug: Cyclophosphamide post transplant; Radiation: Total body 200cGy; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Busulfan

Interventions

Sirolimus DRUG

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).

Also known as: Rapamycin

CGD Recipient

Donor peripheral blood stem cells. BIOLOGICAL

Infuse donor graft.

CGD Recipient

Cyclophosphamide post transplant DRUG

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

Also known as: Cytoxan post transplant

CGD Recipient

Total body 200cGy RADIATION

Day -1

CGD Recipient

Cyclophosphamide DRUG

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

Also known as: Cytoxan

CGD Recipient

Fludarabine DRUG

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

Also known as: Fludara

CGD Recipient

Busulfan DRUG

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

Also known as: Busulfex

CGD Recipient

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 18489989 BACKGROUND

• 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.

  PMID: 21921045 BACKGROUND

• 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.

  PMID: 22053277 BACKGROUND

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Interventions

Sirolimus; Cyclophosphamide; fludarabine; fludarabine phosphate; Busulfan

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Elizabeth Kang
• Organization: NIAID

ekang@niaid.nih.gov

3014027567

Study Officials

• Elizabeth M Kang, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 5, 2014
• Study Start: October 23, 2014
• Primary Completion: April 10, 2019
• Study Completion: December 10, 2019
• Last Updated: May 12, 2020
• Results First Posted: May 1, 2020

Record last verified: 2019-12-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)