Haploidentical Transplant for People With Chronic Granulomatous Disease (CGD) Using Alemtuzumab, Busulfan and TBI With Post-Transplant Cyclophosphamide

NCT03910452 | Active Not Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 19008019-I-0080
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background: CGD causes infections and inflammation. The only cure currently is a bone marrow transplant. Most often a perfectly matched bone marrow donor is used. Researchers want to see if they can lower the risks of using a mismatched donor. Objectives: To see if it is safe to use a related bone marrow donor who is only a partial match to a person with CGD. To see how well drugs given to a person before and after transplant help the body accept the transplant. Eligibility: People ages 4-65 with CGD for whom stem cell transplant may be a cure and who do not have a perfectly matched donor, related or unrelated. Design: Participants will be screened with: Medical history Physical exam Blood tests Participants will be admitted to the hospital about 2 weeks before the transplant. They will have blood, urine, breathing, and heart tests. They may have CT and/or MRI scans. They will have a needle inserted into their hipbone to remove marrow. They will have dental, neurologic, and psychologic tests. They will have a central catheter placed: A line will be placed into a vein in their upper chest. They will get drugs, chemotherapy, and radiation to prepare for the transplant. Participants will receive the donated cells through their catheter. The cells will be from one of their relatives. Participants will stay in the hospital about 6 weeks after the transplant. After they leave the hospital, participants will have to stay in the area with visits about 2 times a week for approximately 100 days post transplant. Then visits will be every 3 to 6 months for 2 years. Then visits will be once a year.

Conditions

Chronic Granulomatous Disease

Keywords

Haplo-identical; Allogeneic Stem Cell Transplant; Peripheral Blood Stem Cell Transplant; Graft Versus Host Disease; Non-Myeloablative Conditioning Regimen

Outcome Measures

Primary Outcomes (1)

• Engraftment - Chimerism

  Myeloid chimerism \>50% without incurring grade 3 steroid refractory or any grade 4 acute graft versus host disease or severe extensive chronic graft versus host disease post transplant.

  Day 30, 100, 6mo, 12 mo

Secondary Outcomes (3)

• Viral immune titrels

  6 mo, 1 year, 2 year, and 3 years post transplant.

• Overall Survival/Event-Free survival

  continuous observation/Day +14, 30, 60, 100, 6 mo, 12 mo, 18 mo, 2,3,4,5 years

• DHR as a marker of normal neutrophil function

  Day 30, 100, 6 month and 1 year

Study Arms (1)

1

EXPERIMENTAL

This is a single arm open-label pilot study.

Drug: Busulfan; Drug: Alemtuzumab; Drug: Cyclophosphamide; Drug: Sirolimus; Radiation: Total Body Irradiation; Biological: Allogeneic peripheral blood stem cell

Interventions

Busulfan DRUG

3 days of IV Busulfan. An alkylating chemotherapeutic agent determined to have broad myelosuppressive effects. On this study is being used as part of conditioning regimen for myelosuppressive properties as per package insert and standard of care.

1

Alemtuzumab DRUG

5 days of IV Alemtuzumab. A humanized monoclonal antibody directed against CD52 (which is abundantly expressed on all human lymphocytes), and causes T cell activation in vitro as well as complement-mediated lysis and antibody-dependent cellular toxicity. For this study, being used as part of the conditioning regimen per package insert and standard of practice.

1

Sirolimus DRUG

Post Peripheral blood stem cell infusion. It is used for its immunosuppressive mechanism of action.

1

Cyclophosphamide DRUG

2 days of IV Cyclophosphamide. This is an antineoplastic, and for this study is bine used for its immunosuppressive mechanism of action per package insert and standard of care

1

Total Body Irradiation RADIATION

2 fractionated doses on -2 day. It is used for its immunosuppressive mechanism of action. It is SOP for conditioning for transplant.

1

Allogeneic peripheral blood stem cell BIOLOGICAL

IV infused donor peripheral blood stem cell. Stem cells are cells that give rise to the blood cells - red blood cells that carry oxygen, white blood cells that help the body to fight infections, and platelets that help make the blood clot. Collected and infused per the standard of operating procedures established by the Department of Transfusion Medicine.

1

Eligibility Criteria

• Age: 4 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. (History of one or more life threatening infections and/or an ongoing infection not responsive to current medical therapy and/or ongoing inflammation along with an oxidase level within quartile 1 or 2.
• Patients will be reviewed at a multidisciplinary meeting for assessment of the risk/benefit ratio of transplant for the patient to determine suitability for this high risk treatment. This multidisciplinary meeting is a combined NCI/NIAID bimonthly meeting comprised of investigators from multiple branches of the NC and NIAID to review patients with immunodeficiencies being considered for various transplant protocols.

You may not qualify if:

• Patients who are 4 65 years of age.
• HLA mismatched related (more than 1 mismatch) 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 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 with 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.
• NOTE: Alemtuzumab (IV formulation) is no longer distributed commercially. In order to receive product, the physician must contact the program for the patient. If the subject is not willing to consent to submit their info (address, date of birth and gender) to the program such that we can obtain the drug, then we cannot proceed with conditioning therefore no transplant will occur on this protocol.
• Participation of Women:
• Contraception: The effects of the combination of conditioning medications (alemtuzumab, busulfan, cyclophosphamide and mycophenolate mofetil) and total body irradiation on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post transplant. Females of childbearing-age must have a negative pregnancy test result prior to receiving any chemotherapy or conditioning agents. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately.
• Participation of Children:
• Children greater than or equal to 4 years of age may participate in this study.
• The subject cannot have a 9/10 or 10/10 HLA matched related or unrelated donor.
• Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater than or equal to 3
• Patients with inflammatory bowel disease deemed in the severe category (severe colitis), because they are at higher risk for GvHD, will be excluded from the protocol until there are 10 patients without severe colitis that have successfully completed a regimen, as determined by engraftment and acute GvHD of a maximum of grade 2. Severity of colitis will be determined in consultation with a gastroenterologist specialist. However, severe colitis will be evaluated within 4 months of transplant and defined as any of the following (where this screening may be performed on a natural history or screening protocol):

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Marsh RA, Kim MO, Liu C, Bellman D, Hart L, Grimley M, Kumar A, Jodele S, Myers KC, Chandra S, Leemhuis T, Mehta PA, Bleesing JJ, Davies SM, Jordan MB, Filipovich AH. An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism following reduced-intensity conditioning hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Biol Blood Marrow Transplant. 2013 Nov;19(11):1625-31. doi: 10.1016/j.bbmt.2013.09.001. Epub 2013 Sep 10.

  PMID: 24035782 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

• Parta M, Kelly C, Kwatemaa N, Theobald N, Hilligoss D, Qin J, Kuhns DB, Zerbe C, Holland SM, Malech H, Kang EM. Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: a Single-Center Prospective Trial. J Clin Immunol. 2017 Aug;37(6):548-558. doi: 10.1007/s10875-017-0422-6. Epub 2017 Jul 28.

  PMID: 28752258 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Granulomatous Disease, Chronic; Graft vs Host Disease

Interventions

Busulfan; Alemtuzumab; Cyclophosphamide; Sirolimus; Whole-Body Irradiation

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Elizabeth M Kang, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 10, 2019
• Study Start: October 28, 2019
• Primary Completion (Estimated): June 15, 2034
• Study Completion (Estimated): June 15, 2034
• Last Updated: April 29, 2026

Record last verified: 2025-09-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)