High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease

NCT02629120 | Active Not Recruiting Phase 1

• 2 other identifiers: 16003216-I-0032
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic granulomatous disease (CGD) affects white blood cell function. Currently, the only curative treatment is bone marrow transplant to replace the abnormal stem cells with new ones (donor cells) capable of making a normal immune system. Transplant problems include graft versus host disease (GvHD) and graft rejection. With GvHD, donor cells attack the recipient s normal tissue. Researchers want to use preparation drugs and a high cell dose to increase graft success. They want to use 2 immunosuppressive drugs (cyclophosphamide and sirolimus) to lessen the risk of GvHD.

Conditions

Chronic Granulomatous Disease Transplant

Keywords

The National Marrow Donor Program (NMDP); Matched Unrelated Donor (MUD); HLA Matched Related Donor

Outcome Measures

Primary Outcomes (1)

• To determine engraftment rates with the use of high cell doses, without increasing the risk of GvHD by using post-transplant cyclophosphamide and sirolimus in conjunction with a busulfan- based conditioning regimen. We will compare the incidence...

  This study is still recruiting patients.

  5 years

Secondary Outcomes (3)

• To measure the engraftment rate and the engraftment kinetics using such a regimen

  5 years

• To assess the level and kinetics of immune reconstitution (via chimerism) when using post- transplant cyclophosphamide

  5 years

• To further elucidate the factors involved in the development of GvHD and graft rejection/failure

  5 years

Study Arms (1)

1

ACTIVE COMPARATOR

There is only one treatment arm for this study

Drug: Alemtuzumab; Drug: Busulfan; Drug: Sirolimus; Drug: Cyclophosphamide; Radiation: Total Body Irradiation; Biological: Peripheral blood stem cells

Interventions

Alemtuzumab DRUG

Transplant Conditioning Drug: Monoclonal antibody that targets recipient and donor T-cells to prevent graft verses host disease. Not an IND. This is a well studied drug, and is not under an IND.

1

Busulfan DRUG

Transplant Conditioning Drug: Chemotherapy to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow. This is a well studied drug, and is not under an IND.

1

Total Body Irradiation RADIATION

Transplant Conditioning Total Body Radiation (300cGy in 2 fractionated doses), given only to patient receiving matched unrelated donor cells, to create space in the patient's bone marrow so that the donor peripheral blood stem cells can repopulate in the patient's bone marrow.

1

Peripheral blood stem cells BIOLOGICAL

Donor Peripheral blood stem cells, either matched unrelated donor or matched related relative to replace the patient's immune cells with functional immune cells. The peripheral blood stem cells are not regulated by the FDA.

1

Sirolimus DRUG

Immunosuppressant to prevent donor peripheral blood stem cell rejection and graft versus host disease. This is a well studied drug, and is not under an IND.

1

Cyclophosphamide DRUG

Post transplant cyclophosphamide given to prevent graft verses host disease. This is a well studied drug, and is not under an IND.

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 confirmed Chronic Granulomatous Disease.
• 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 or have a Quartile 1 and/or 2 residual oxidase production level.
• Ages 4 years - 65 years
• HLA-matched family donor graft or an HLA matched unrelated peripheral blood stem cell (PBSC) graft (10/10 or 9/10 mismatch) available
• Must be HIV negative
• When discharged from the hospital 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 -200 NIH Durable Power of Attorney for Health Care Decision Making .
• If of child-bearing potential, must agree to consistently use contraception from one month prior to, and throughout, study participation, and for 3 months post-study. Acceptable forms of contraception are:
• Contraceptive pills or patch, Norplant , Depo-Provera , 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.

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) or equivalent performance status greater than or equal to 3 (See Supportive Care guidelines, available at http://intranet.cc.nih.gov/bmt/clinicalcare)
• Left ventricular ejection fraction \< 40%
• Transaminases \> 5x upper limit of normal based on the participant 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 making regulatorily and legally effective informed consent impossible
• Major anticipated illness or organ failure incompatible with survival from AlloPBSC transplant
• Pregnant or lactating
• HIV positive
• Uncontrolled seizure disorder
• Individuals older than 65 are excluded. It is known from standard transplantation that these participants 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 participants at this time.
• Any condition or circumstance which 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) 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. In order 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.
• Patients with a CRP greater than 100 mg/L within 30 days of anticipated transplant.
• If the underlying inflammation is controlled for one month with repeat CRP testing showing a level of less than 100 on at least two separate testings, the patient will be reconsidered for transplant. If during this time period a CRP of greater than 100 is measured, then the patient would no longer be eligible for transplant.

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)

• Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S, Peggs K, Verfuerth S, Pettengell R, Marsh JC, Schey S, Mahendra P, Morgan GJ, Hale G, Waldmann H, de Elvira MC, Williams CD, Devereux S, Linch DC, Goldstone AH, Mackinnon S. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000 Oct 1;96(7):2419-25.

  PMID: 11001893 BACKGROUND

• Kang EM, Hsieh MM, Metzger M, Krouse A, Donahue RE, Sadelain M, Tisdale JF. Busulfan pharmacokinetics, toxicity, and low-dose conditioning for autologous transplantation of genetically modified hematopoietic stem cells in the rhesus macaque model. Exp Hematol. 2006 Feb;34(2):132-9. doi: 10.1016/j.exphem.2005.10.010.

  PMID: 16459181 BACKGROUND

• Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA, Leitman SF, Read EJ, Malech HL. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001 Mar 22;344(12):881-8. doi: 10.1056/NEJM200103223441203.

  PMID: 11259721 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Macrolides; Lactones; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; 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: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 14, 2015
• Study Start: December 17, 2015
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 20, 2026

Record last verified: 2025-06-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data availability and the duration of the data availability are as follows:@@@@@@@@@@@@Transplant data shared with CIBMTR, BTRIS, and the NML will be shared at the onset of signing the protocol and will be maintained in shared databases with no end date. @@@@@@@@@@@@Transplant data submitted for publication will be immediately available following publication with no end date.
• Access Criteria: IIndividual deidentified data will be shared with: @@@The Center for International Blood and Transplant Research (CIBMTR), as required by the Stem Cell Therapeutic and Research Act of 2005 https://www.congress.gov/bill/109th-congress/house-bill/2520 @@@An NIH-funded or approved public repository. @@@Publications@@@Public presentations. @@@Individual identified participant data will be shared with: @@@Approved outside collaborators under appropriate agreements, such as the Neutrophil Monitoring Lab (NML) in Frederick, Md.@@@Biomedical Translational Research Information System (BTRIS).@@@The following related documents will be available:@@@Study Protocol @@@Statistical analysis plan @@@Analytic code@@@CIBMTR, BTRIS, and the NML data will be shared at the onset of signing the protocol and will be maintained in shared databases with no end date. @@@Data submitted for publication will be immediately available following publication with no end date.@@@

Locations

US (1)