We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02629120
Recruitment Status : Recruiting
First Posted : December 14, 2015
Last Update Posted : November 3, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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.

Condition or disease Intervention/treatment Phase
Chronic Granulomatous Disease Transplant Drug: Alemtuzumab Drug: Busulfan Drug: Sirolimus Drug: Cyclophosphamide Radiation: Total Body Irradiation Biological: Peripheral blood stem cells Phase 1 Phase 2

Detailed Description:

Study Description:

Alemtuzumab, targeted busulfan, and TBI, with a 10/10 related or MUD donor graft or a 9/10 single HLA mismatch graft followed by post-transplant cyclophosphamide.

Primary Objectives:

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 of graft rejection/failure and GvHD to the incidence obtained from Protocol 07-I-0075.

Secondary Objectives:

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

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

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

To evaluate the risk of viral infections in the setting of Alemtuzumab (Campath-1H) and post-transplant cyclophosphamide.

Primary Endpoint:

Reduced incidence of graft failure or rejection (as defined by >20% engraftment by oxidase- positive neutrophils in at least 95% of participants by Day 100, 6 months, and 1 year post BMT) will be assessed as event-free survival (EFS). Graft failure will result in disease recurrence. This will be assessed in a composite form along with GvHD (see Biostatistical Considerations section 17).

Secondary Endpoints:

Same or reduced rate of grade 3-4 aGvHD of <20% .

Establish stable mixed chimerism.

Improve rapidity of immune reconstitution.

Overall survival.

Tertiary Endpoints:

Evaluation of inflammatory markers as risk factors for

engraftment syndrome

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: High Dose Peripheral Blood Stem Cell Transplantation With Post Transplant Cyclophosphamide for Patients With Chronic Granulomatous Disease
Actual Study Start Date : December 17, 2015
Estimated Primary Completion Date : November 30, 2026
Estimated Study Completion Date : November 30, 2026


Arm Intervention/treatment
Active Comparator: 1
There is only one treatment arm for this study
Drug: Alemtuzumab
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.

Drug: Busulfan
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.

Drug: Sirolimus
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.

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

Radiation: Total Body Irradiation
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.

Biological: Peripheral blood stem cells
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.




Primary Outcome Measures :
  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... [ Time Frame: 5 years ]
    This study is still recruiting patients.


Secondary Outcome Measures :
  1. To measure the engraftment rate and the engraftment kinetics using such a regimen [ Time Frame: 5 years ]
    This study is still recruiting patients

  2. To assess the level and kinetics of immune reconstitution (via chimerism) when using post- transplant cyclophosphamide [ Time Frame: 5 years ]
    This study is still recruiting patients

  3. To further elucidate the factors involved in the development of GvHD and graft rejection/failure [ Time Frame: 5 years ]
    This study is still recruiting patients



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   4 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • 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.

EXCLUSION CRITERIA:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02629120


Contacts
Layout table for location contacts
Contact: Corin Kelly, R.N. (301) 761-1772 ckelly2@niaid.nih.gov
Contact: Elizabeth M Kang, M.D. (301) 402-7567 ekang@niaid.nih.gov

Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Layout table for investigator information
Principal Investigator: Elizabeth M Kang, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02629120    
Other Study ID Numbers: 160032
16-I-0032
First Posted: December 14, 2015    Key Record Dates
Last Update Posted: November 3, 2022
Last Verified: October 31, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .The following data will be shared: @@@@@@All the individual participant data collected during the trial, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.@@@

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
The National Marrow Donor Program (NMDP)
Matched Unrelated Donor (MUD)
HLA Matched Related Donor
Additional relevant MeSH terms:
Layout table for MeSH terms
Granuloma
Granulomatous Disease, Chronic
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Sirolimus
Cyclophosphamide
Busulfan
Alemtuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents, Immunological