RIC + BMT for Non-Malignant Disorders
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Washington University School of Medicine
Disqualifiers: HLA-identical sibling donor, Cirrhosis, Uncontrolled infection, HIV, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you have received an investigational drug or device within 3 months of enrollment, you may not be eligible to participate.
What data supports the effectiveness of the treatment RIC + BMT for Non-Malignant Disorders?
Research shows that reduced-intensity conditioning (RIC) is effective in making stem cell transplants safer for older or less healthy patients by lowering treatment-related deaths. This approach has been successful in treating blood cancers, suggesting it might also be beneficial for non-malignant disorders.12345
Is the reduced-intensity conditioning (RIC) regimen generally safe for humans?
Reduced-intensity conditioning (RIC) regimens are designed to be less harsh than traditional high-dose treatments, aiming to reduce side effects and complications. They are generally considered to have lower toxicity and are safer for patients who cannot tolerate more intense treatments, although they still carry some risks.24567
How is the RIC + BMT treatment different from other treatments for non-malignant disorders?
The RIC (Reduced-Intensity Conditioning) regimen is unique because it uses lower doses of chemotherapy and radiation to prepare the body for a bone marrow transplant, reducing the risk of severe side effects. This makes it suitable for older patients or those with other health issues who might not tolerate more intense treatments.12348
Eligibility Criteria
This trial is for young people (up to age 20.99) with non-malignant disorders like sickle cell disease, bone marrow failure, or metabolic diseases. They must have specific health criteria met such as normal kidney function and no severe liver issues. Participants need a performance score of at least 50 and agree to contraception methods post-transplant.Inclusion Criteria
My kidney function is within the normal range.
I have had multiple severe episodes of acute chest syndrome.
Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.
See 17 more
Exclusion Criteria
I have an active autoimmune disease like lupus.
I have a sibling who matches my bone marrow and is willing to donate.
I haven't used any experimental drugs or devices in the last 3 months.
See 5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Reduced Intensity Conditioning
Participants receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan
3 weeks
Bone Marrow Transplantation
Participants undergo familial HLA-mismatched bone marrow transplantation
1 week
Follow-up
Participants are monitored for safety and effectiveness after transplantation, including donor cell engraftment and organ function
2 years
Multiple visits at 90 days, 180 days, 1 year, and 2 years post-transplant
Treatment Details
Interventions
- GVHD prophylaxis regimen (Immunosuppressant)
- RIC regimen (Chemotherapy)
Trial OverviewThe study tests the effectiveness and safety of familial HLA mismatched bone marrow transplants in patients under 21 with non-cancerous diseases. It includes a reduced intensity conditioning (RIC) regimen before transplant and graft-versus-host disease (GVHD) prevention afterwards.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: RIC Prep Regimen & GVHD ProphylaxisExperimental Treatment2 Interventions
Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen
RIC regimen is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Reduced-Intensity Conditioning for:
- Bone Marrow Failure Syndromes
- Myelodysplastic Syndrome
- Acute and Chronic Myeloid Leukemias
- Metabolic Disorders
🇺🇸 Approved in United States as Reduced-Intensity Conditioning for:
- Immune Deficiencies
- Pre-Leukemia Syndromes
- Acute Myeloid Leukemia
- Chronic Myeloid Leukemia
- Metabolic Disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Yale School of MedicineNew Haven, CT
Helen DeVos Children's HospitalGrand Rapids, MI
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
Washington University School of MedicineLead Sponsor
References
Reduced intensity versus myeloablative allogeneic stem cell transplantation for the treatment of acute myeloid leukemia, myelodysplastic syndrome and acute lymphoid leukemia. [2011]Use of a reduced intensity conditioning (RIC) regimen has now become standard practice among older or more infirmed stem cell transplantation candidates. Encouraging outcome in this population has led to the question of whether RIC should replace standard myeloablative conditioning (MAC) regimens. This review will summarize the available outcomes data comparing RIC and MAC approaches to stem cell transplantation in adult patients with acute myeloid leukemia, myelodysplastic syndrome (MDS) and acute lymphoid leukemia.
A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation. [2021]Nonmyeloablative (NM) conditioning and reduced-intensity conditioning (RIC) are increasingly used for allogeneic hematopoietic stem-cell transplantation. Such regimens have not been compared.
Reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation. [2007]Chemotherapy and radiotherapy administered in preparation for allogeneic hematopoietic progenitor cell transplantation serve the dual role of providing antitumor activity as well as immunosuppression to prevent graft rejection. Conditioning regimens were initially designed to provide dose-intense therapy in order to overcome tumor resistance. These forms of transplants, referred to as ablative regimens, often result in significant extramedullary toxicity, limiting its applicability to younger, fitter patients. Reduced-intensity conditioning (RIC) transplants are a direct result of an understanding of the immunotherapeutic potential of the donated hematopoietic stem cells. These forms of transplants administer chemoradiotherapy with the intent of allowing for donor cell engraftment with less of an emphasis on dose intensity. In so doing, treatment-related mortality has been reduced, and older-aged patients and those with co-morbidities are now frequently offered this therapy. In the decade since its creation, RIC transplantation has changed the spectrum of patients with malignancies who may benefit from this therapy. For the first time, transplant patients are becoming more representative of the populations most at risk for diseases requiring this therapy. This article reviews the science behind RIC transplants and provides a concise summary of the current body of evidence for the major indications for which it is most commonly employed. The data presented will demonstrate that age should no longer be the sole deciding factor for referral for allogeneic transplant.
Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. [2009]Reduced intensity conditioning regimen (RIC) is increasingly used in hematopoietic stem cell transplantation (HSCT). Unrelated donor (UD) transplants have more complications. We wanted to examine if RIC is a valid treatment option using UD in acute myeloblastic leukemia (AML).
Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. [2013]Reduced-intensity conditioning (RIC) for allogeneic stem-cell transplantation (allo-SCT) reduces nonrelapse mortality (NRM). This reduction makes it possible for patients who are ineligible for high-dose myeloablative conditioning allo-SCT to benefit from graft-versus-leukemia reaction. In this multicenter, prospective study of patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of RIC allo-SCT from a human leukocyte antigen-identical sibling by using a regimen that uses fludarabine and busulfan.
Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. [2022]During the 2006 BMT Tandem Meetings, a workshop was convened by the Center for International Blood and Marrow Transplant Research (CIBMTR) to discuss conditioning regimen intensity and define boundaries of reduced-intensity conditioning (RIC) before hematopoietic cell transplantation (HCT). The goal of the workshop was to determine the acceptance of available RIC definitions in the transplant community. Participants were surveyed regarding their opinions on specific statements on conditioning regimen intensity. Questions covered the "Champlin criteria," as well as operational definitions used in registry studies, exemplified in clinical vignettes. A total of 56 participants, including transplantation physicians, transplant center directors, and transplantation nurses, with a median of 12 years of experience in HCT, answered the survey. Of these, 67% agreed that a RIC regimen should cause reversible myelosuppression when administered without stem cell support, result in low nonhematologic toxicity, and, after transplantation, result in mixed donor-recipient chimerism at the time of first assessment in most patients. Likewise, the majority (71%) agreed or strongly agreed that regimens including
Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents. [2013]The realization in the 1990s that allogeneic stem cell transplants (SCT) have a potentially curative graft-versus-leukemia (GVL) effect in addition to the antileukemic action of myeloablative conditioning regimens was a major stimulus for the development of reduced-intensity conditioning (RIC) regimens, aimed primarily at securing engraftment to provide the GVL effect, while minimizing regimen-related toxicity. It is now over 10 years since RIC regimens were heralded as a new direction in the field of SCT. Over the last decade much has been learned about the ways in which the conditioning regimen can be tailored to provide adequate immunosuppression, and modulated to deliver a chosen degree of antimalignant treatment. The huge literature of clinical data with RIC transplantation now permits us to more clearly define the success and limitations of the approach. This review examines the origins of RIC SCT, explores the degree to which the initial expectations and purpose of the approach have been realized, and outlines some ways forward for the field.
Reduced intensity conditioning and allogeneic stem cell transplantation in childhood malignant and nonmalignant diseases. [2010]Allogeneic hematopoietic SCT is well established as a potentially curative therapy for children and adults with both malignant and nonmalignant diseases. However, myeloablative SCT is associated with significant short- and long-term complications. The goals of a reduced intensity-conditioning (RIC) regimen are to prevent graft rejection and establish stable donor-derived hematopoiesis at a level sufficient for cure of the underlying disease and, in patients with hematologic malignancy, to provide a GVL effect, while decreasing the short- and long-term complications associated with myeloablative conditioning therapy. RIC regimens have enabled SCT to be performed in children with preexisting comorbidities that preclude conventional conditioning. RIC-SCT has been most extensively studied in patients with nonmalignant disorders and for some of these, including primary immunodeficiencies and hemophagocytic lymphohistiocytosis, sufficient data now exist to support its routine use even in patients without comorbidity. Less data exist on RIC-SCT for children with hematologic malignancies and at present this should be restricted to children who are not candidates for, or have relapsed after, myeloablative SCT. Here we review available data on the use of RIC-SCT in pediatric patients, highlighting important clinical lessons and areas that require further study.