Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease (CGD) With an Alemtuzumab, Busulfan and TBI-based Conditioning Regimen Combined With Cytokine (IL-6, +/- IFN-gamma) Antagonists

• Status: Recruiting
• Trial end date: 2032-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Background:

Chronic granulomatous disease (CGD) affects the immune system. People with CGD are more likely to get infections. Drugs can help control infections, but these treatments can cause side effects including kidney failure and deafness. Stem cell transplants can cure CGD, but these don t always work.

Objective:

To find out if a different drug treatment can improve the success rates of stem cell transplants in people with CGD.

Eligibility:

People aged 4-65 years with CGD.

Design:

Participants will undergo screening. They will have a physical exam. They will have blood and urine tests and tests of their heart function and breathing. They will have imaging scans. They will have a bone marrow biopsy; a needle will be inserted into their hip to draw a sample of tissue from the bone.

A tube called a catheter will be placed into a vein in the participant s chest. This catheter will remain in place for the transplant and recovery period. Blood for tests can be drawn from the catheter, and medications and the stem cells can be administered through it.

Participants will be in the hospital for either 10 or 21 days to receive 3 or 4 drugs before the transplant. They will get 2 doses of total body radiation on the same day.

Participants will receive donor stem cells through the catheter. They will remain in the hospital for 6 weeks afterward.

Participants will visit the clinic 2 to 3 times per week for 3 months after discharge.

Follow-up visits will continue for 5 years.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Alemtuzumab; Busulfan; Cyclophosphamide; Sirolimus

Criteria

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all the following criteria:

• Must have the ability to comprehend and a willingness to sign the informed consent. For pediatric patients, must have a parent/guardian who can sign consent if the donor is a minor; assent will be obtained from minors as appropriate.

• Must have confirmed diagnosis of CGD.

• Must have sufficient complications from underlying disease to warrant undergoing transplantation (either a history of or ongoing inflammation/CGD-related autoimmunity OR a CGD-related infection while on prophylaxis) OR have a Quartile 1 or 2 residual oxidase production level.

• Ages 4 years-65 years.

• HLA-matched family donor graft or an HLA-matched unrelated PBSC graft (10/10 or 9/10 mismatch) available.

• Must be human immunodeficiency virus (HIV) negative.

• When discharged from the hospital the participant must be able to stay within 1 hour s travel of the NIH for the first 3 months after transplantation.

• Must have a family member or other designated care provider to assist with care during the post-transplant period when the patient is in the outpatient setting.

• Must provide a durable power of attorney for health care decisions to an appropriate adult relative or guardian in accordance with NIH 200 NIH Durable Power of Attorney for Health Care Decision Making.

• Females of child-bearing potential must agree to consistently use one form of contraception from 1 month prior to study entry and for at least 1 year post transplant. Male participants must agree to consistently use contraception for 1 year post transplant. Acceptable forms of contraception are:

• Contraceptive pills or patch, Norplant [Registered], Depo-Provera [Registered], or other FDA-approved contraceptive method.

• Male partner has previously undergone a vasectomy.

• Male participants will be advised to consistently use contraception throughout study participation and for 3 months post-transplant.

• Stated willingness to comply with all study procedures and is available for protocol visits for the duration of the study when possible.

• Patients who have a CRP of greater than 100 but otherwise meet inclusion criteria will be enrolled on the high-risk arm.

• CRP will be assessed no more than 7 weeks and no less than 6 weeks prior to anticipated transplant to determine on which arm the patient will be treated.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Ejection fraction of less than 30% by echocardiography.

• Forced expiratory volume (FEV1%) of less than 35% and/or an adjusted diffusing capacity of lung of carbon monoxide (adj DLCO) of less than 30%.

• Transaminases >5x upper limit of normal based on the individual s clinical situation and at the discretion of the investigator.

• Psychiatric disorder or mental deficiency severe enough as to make compliance with the HSCT treatment unlikely, and/or to make regulatorily and legally effective informed consent impossible.

• Major anticipated illness or organ failure incompatible with survival from allogeneic peripheral blood stem cell (AlloPBSC) transplant.

• Pregnant or lactating.

• Uncontrolled seizure disorder per principal investigator (PI) discretion.

• Individuals older than 65 years are excluded. It is known from standard transplantation that these individuals have a higher risk of morbidity and mortality related to transplantation. Given the investigational nature of this protocol, the risk-benefit ratio is not warranted to include these individuals at this time.

• Active TB infection.

• Any condition or circumstance that the PI feels would create difficulty in maintaining compliance with the requirements of this protocol.

• Individuals who are not willing to submit their information as part of the alemtuzumab (Campath [Registered]) Distribution Program application or participants whom the Distribution Program committee has determined are not qualified to receive alemtuzumab.

NOTE: Alemtuzumab (Campath-1H) (intravenous [IV] formulation) is no longer distributed commercially. To receive product, the physician must contact the program for the patient. If the patient is not willing to consent to submit their info (demographics, contact information, and rationale for use) to the program such that we can obtain the drug, then we cannot proceed with conditioning; therefore no transplant will occur on this protocol. http://www.campath.com/