Bone Marrow Transplant for Immune Deficiency
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Investigational agents
Disqualifiers: HIV, Active psychiatric disorder, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems.
Objective:
To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies.
Eligibility:
Donors: Healthy people ages 4 or older
Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Participants will have urine tests, EKG, and chest x-ray.
Donors will have:
Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone.
OR
Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm.
Possible vein assessment or pre-anesthesia evaluation
Recipients will have:
Lung test, heart tests, radiology scans, CT scans, and dental exam
Possible tissue biopsies or lumbar puncture
Bone marrow and a small piece of bone removed by needle in the hipbone.
Chemotherapy 1-2 weeks before transplant day
Donor stem cell donation through a catheter put into a vein in the chest or neck
Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures.
After discharge, recipients will:
Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission.
Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years....
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, since chemotherapy is involved, it's possible that some medications might need to be adjusted. Please discuss this with the trial team for specific guidance.
What data supports the effectiveness of the treatment Allo BMT for immune deficiency?
Allogeneic bone marrow transplantation (Allo BMT) is considered an effective treatment for various immune deficiency disorders, as it is the only cure for many primary immune deficiency disorders and inherited bone marrow failure syndromes. Studies have shown that it is also effective for severe combined immunodeficiency (SCID), with a high survival rate in patients receiving HLA-identical transplants.
12345Is allogeneic bone marrow transplantation generally safe for humans?
Allogeneic bone marrow transplantation (BMT) can be risky, with potential complications like graft failure, graft-versus-host disease (GVHD), and infections. Long-term effects may include lung problems, cataracts, and other health issues. While it can be life-saving for certain conditions, it is associated with significant risks and is usually done in specialized centers.
16789How is the treatment Allo BMT different from other treatments for immune deficiency?
Allo BMT is unique because it involves transplanting healthy bone marrow from a donor to replace the patient's faulty immune system, offering a potential cure for many immune deficiencies. Unlike other treatments that may only manage symptoms, this approach aims to restore normal immune function by using donor stem cells.
210111213Eligibility Criteria
This trial is for people aged 4-75 with primary immunodeficiencies that could be treated by a blood or marrow transplant. Donors must be healthy and at least 4 years old. Participants need to have certain immune system issues, like severe infections or autoimmune diseases, and good organ function. Pregnant women can't join, and participants must agree to use contraception for one year post-transplant.Inclusion Criteria
I am between the ages of 4 and 75.
I have a donor who is a close match to my tissue type.
Ability to understand and sign a written informed consent document
+5 more
Exclusion Criteria
I have had a condition where my lymphocytes grow abnormally.
Lack of adequate central venous access potential
I haven't had any cancer except for skin cancer in the last 5 years.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Pre-transplant Conditioning
Recipients undergo chemotherapy 1-2 weeks before transplant day
1-2 weeks
Inpatient stay
Transplantation
Donor stem cell donation and transplantation procedure
1 day
Inpatient procedure
Post-transplant Hospitalization
Several-week hospital stay for monitoring and treatment post-transplant
Several weeks
Inpatient stay
Initial Follow-up
Participants remain near the clinic for about 3 months with weekly visits
3 months
Weekly visits (in-person)
Long-term Follow-up
Multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years
5 years
Regular visits (in-person)
Participant Groups
The trial tests if blood or bone marrow transplants from donors are safe and effective in treating various primary immunodeficiencies. It involves screening, pre-transplant assessments, chemotherapy before the transplant day, hospital stay for several weeks with follow-up visits up to five years.
6Treatment groups
Experimental Treatment
Active Control
Group I: 6/ RIC-SHORT ArmExperimental Treatment3 Interventions
Reduced Intensity Conditioning with shortened duration and dose-reduced PTCy
Group II: 4/ RIC-MMF ArmExperimental Treatment3 Interventions
Reduced Intensity Conditioning with MMF duration de-escalation design
Group III: 3/ MAC Arm-Closed with amendment L (07/05/2019)Experimental Treatment3 Interventions
Myeloablative Conditioning Arm
Group IV: 2/ RIC Arm - Closed with Amendment L (07/05/2019)Experimental Treatment3 Interventions
Reduced Intensity Conditioning Arm
Group V: 1/ IOC Arm-Closed with amendment L (07/05/2019)Experimental Treatment3 Interventions
Immunosuppression Only Conditioning Arm
Group VI: 5/ Donor ArmActive Control1 Intervention
Donor
Allo BMT is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Allogeneic Blood or Marrow Transplantation for:
- Primary Immunodeficiencies
- Severe Combined Immunodeficiency
- Wiskott-Aldrich Syndrome
- X-linked Lymphoproliferative Syndrome
🇺🇸 Approved in United States as Allogeneic Blood or Marrow Transplantation for:
- Primary Immunodeficiencies
- Severe Combined Immunodeficiency
- Wiskott-Aldrich Syndrome
- X-linked Lymphoproliferative Syndrome
- Chronic Granulomatous Disease
🇨🇦 Approved in Canada as Allogeneic Blood or Marrow Transplantation for:
- Primary Immunodeficiencies
- Severe Combined Immunodeficiency
- Wiskott-Aldrich Syndrome
- X-linked Lymphoproliferative Syndrome
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Marrow Donor ProgramMinneapolis, MN
National Institutes of Health Clinical CenterBethesda, MD
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Allogeneic bone marrow transplantation in the treatment of hematologic diseases. [2021]The current use of allogeneic bone marrow transplantation in various hematologic diseases is reviewed. Bone marrow transplantation (BMT) involves infusion of bone marrow from a suitable donor into a properly conditioned recipient. Most BMT is allogeneic, in which the donor is genetically dissimilar but shares some common tissue antigens with the recipient. Almost all patients undergoing allogeneic BMT must be "prepared" with high-dose cyclophosphamide to prevent graft rejection. Most patients with hematologic malignancy also receive total body irradiation to eradicate malignant cells located in areas inaccessible to the systemic circulation. Bone marrow transplantation is the treatment of choice for severe aplastic anemia. In acute myelogenous leukemia, the best results are observed in young patients undergoing BMT in first remission. In acute lymphoblastic leukemia, BMT is usually reserved for patients in second or subsequent remission. Early results are promising in patients with chronic myelogenous leukemia who receive BMT before the accelerated phase or blast crisis of this disease. Allogeneic BMT offers an opportunity for cure in some patients with relapses of Hodgkin's disease or those with certain subtypes of non-Hodgkin's lymphoma. Other diseases for which BMT has been used include severe combined immune deficiency disease, Fanconi's anemia, and multiple myeloma. Complications of BMT include graft failure or rejection, acute and chronic graft-versus-host disease, and infectious complications; late complications, such as restrictive and obstructive pulmonary disease, cataracts, sterility, and secondary malignancies, may also occur. Bone marrow transplantation has become an important treatment for many hematologic diseases, but it will probably remain a treatment reserved for only a few highly specialized centers. If morbidity and mortality caused by transplant-related complications can be reduced, BMT may be offered to older patients and those without HLA-identical sibling donors.
Reduced Intensity Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric Inherited Immune Deficiencies and Bone Marrow Failure Syndromes. [2022]Allogeneic bone marrow transplantation (alloBMT) is the only cure for many primary immune deficiency disorders (PIDD), primary immune regulatory disorders (PIRD), and inherited bone marrow failure syndromes (IBMFS).
Current status of allogeneic bone marrow transplantation. [2019]Use of allogeneic bone marrow transplants continues to increase. During the 36-year period between 1955 and 1990, more than 33,000 patients received allogeneic bone marrow transplants; more than 45% of these were performed during the 3 years 1988-1990. Transplants are effective therapy for leukemia and other hematologic diseases. It is widely considered that transplants are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia and a variety of genetic, metabolic and immune deficiency disorders. Successful application of bone marrow transplantation is limited by complications such as graft failure, graft versus host disease GVHD and interstitial pneumonia and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants were performed using unrelated or HLA-partially matched related donors with some success. Development of post-transplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified.
Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the european society for immunodeficiency. [2019]We analyzed the outcomes of 214 HLA non-identical T-cell-depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B-) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome. The disease-free survival was significantly better for patients with B+ SCID (60%) as compared with patients with B- SCID (35%) (P =.002), with a median follow-up of 57 months and 52 months, respectively. Other factors associated with a poor prognosis were the presence of a lung infection before BMT (odds ratio = 2.47 [1.99-2.94]) and the use of monoclonal antibodies for T-cell depletion of the graft (odds ratio = 1.67 [1. 18-2.15]). Additional factors influencing outcome were age at BMT (
European experience of bone-marrow transplantation for severe combined immunodeficiency. [2019]The outcome of bone-marrow transplantations (BMT) carried out between 1968 and March 1, 1989, in 183 patients with severe combined immunodeficiency (SCID) was analysed. Recipients of HLA-identical BMTs (70) had a 76% probability of survival (median follow-up 73 months). Of the 32 treated since 1983, 97% have been cured (median follow-up 41 months). This good prognosis was associated with rapid development of T and B cell function. HLA-non-identical, T-cell-depleted, BMT (n = 100) gave significantly lower survival (52%; median follow-up 47 months). Factors associated with poor prognosis were the presence of a lung infection before BMT, absence of a protected environment, and use of female donors for male recipients. Use of a conditioning regimen significantly increased the frequency of sustained engraftment (86% vs 50% for non-conditioned BMT) and resulted in more frequent engraftment of donor B lymphocytes and myeloid cells. Donor B-cell chimerism was strongly associated with the development of normal B-cell function.
HLA-matched sibling transplantation with G-CSF mobilized PBSCs and BM decreases GVHD in adult patients with severe aplastic anemia. [2021]Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for severe aplastic anemia (SAA). However, graft failure and graft-versus-host disease (GVHD) are major causes of the early morbidity in Allo-HSCT.
Allogeneic HSCT for autoimmune diseases: conventional conditioning regimens. [2007]Allogeneic hematopoietic stem cell transplantation (HSCT) tests the hypothesis that the replacement of a 'diseased' autoreactive immunological and stem cell compartment with one that is not autoreactive (but potentially alloreactive) can cure severe autoimmune diseases. The primary risks of allogeneic HSCT are the morbidity and morality associated with delayed immune reconstitution and GVHD. Although the risk of complications and mortality is greater than autologous HSCT, studies of allogeneic HSCT should be conducted in selected cases because there is a greater potential for sustained remissions. This review will discuss the anticipated results from allogeneic HSCT by summarizing outcomes in aplastic anemia and chronic myelogenous leukemia as well as a brief description of Seattle's experience with allogeneic HSCT in the first two patients with systemic sclerosis.
Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases. [2009]Allogeneic hematopoietic stem cell transplantation (HSCT) offers the unique opportunity to replace a diseased hematopoietic or immune system by healthy donor cells. Proof of principle comes from experimental animal data, from the experience with severe aplastic anemia, from observations of patients with concomitant autoimmune disease and from scattered case reports. Complete remissions have been described as well as failures. Allogeneic HSCT remains associated with significant morbidity and mortality. The potential risks might outweight the benefits. Currently, allogeneic HSCT cannot be recommended in general. Carefully conducted prospective studies are warranted to define target populations and best technology to be used. Conditions for such studies have been identified by an international expert panel.
Long-term treatment burden following allogeneic blood and marrow transplantation in NSW, Australia: a cross-sectional survey. [2022]Allogenic blood and marrow transplant (allo-BMT) is an arduous treatment used increasingly for many life-threatening conditions. Recognition of the profound impacts of the long term and late effects is ever-growing, as is the healthcare workload (treatment burden) of survivorship.
T-cell receptor αβ+ and CD19+ cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. [2022]Allogeneic hematopoietic stem cell transplantation (HSCT) is used as a therapeutic approach for primary immunodeficiencies (PIDs). The best outcomes have been achieved with HLA-matched donors, but when a matched donor is not available, a haploidentical or mismatched unrelated donor (mMUD) can be useful. Various strategies are used to mitigate the risk of graft-versus-host disease (GvHD) and rejection associated with such transplants.
Allogeneic bone marrow transplantation. [2019]Allogeneic bone marrow transplantation (BMT) after high-dose, marrow-ablative chemoradiotherapy has been established as the treatment of choice for various hematologic, neoplastic, and congenital disorders. The most common type of marrow graft is an allogeneic one from a sibling donor who has compatible human leukocyte antigen (HLA). Only 30% of patients requiring allogeneic BMT have an HLA-compatible sibling donor. Over the past few years, marrows from unrelated HLA-compatible donors have been used with increasing frequency and promising outcome in certain hematologic malignancies. Despite the morbidity and mortality associated with this treatment modality, allogeneic BMT may provide a 20% to 90% chance of long-term, disease-free survival to patients with a wide variety of neoplastic and abnormal marrow disorders.
Bone marrow transplantation for severe combined immune deficiency. [2022]Bone marrow transplantation (BMT) using stem cells obtained from a family-related, HLA-identical donor (RID) is the optimal treatment for patients with severe combined immune deficiency (SCID). In the absence of an RID, HLA-mismatched related donors (MMRDs) are often used. However, compared with RIDs, use of MMRDs for BMT is associated with reduced survival and inferior long-term immune reconstitution. Use of HLA-matched unrelated donors (MUDs) represents another potential alternative for BMT.
Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia. [2023]Allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor is recommended as an initial treatment for young patients. However, immunosuppressive therapy (IST) with cyclosporine and anti-thymocyte globulin may be a viable option even when an HLA-identical sibling donor is available.