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

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Jul 15, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach to improve the success of stem cell transplants for people with Chronic Granulomatous Disease (CGD), a condition that affects the immune system and makes it harder to fight infections. The study will involve participants aged 4 to 65 who have been diagnosed with CGD and have significant health issues related to the disease. To join, participants need to have a compatible donor for the stem cell transplant and must be free of certain health problems.

During the trial, participants will undergo a series of tests to ensure they are suitable for the procedure. They will spend 10 to 21 days in the hospital receiving treatment before the transplant, which includes specific medications and radiation. After receiving the donor stem cells, they will stay in the hospital for about 6 weeks and continue with regular visits to the clinic for three months, with follow-up visits for up to five years. It's important to have a family member or caregiver available to help during recovery. This trial aims to enhance the effectiveness of stem cell transplants, potentially offering a better chance for a cure for CGD.

Gender

ALL

Eligibility 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/