Umbilical Cord Blood Transplant for Aplastic Anemia and Myelodysplastic Syndrome
Recruiting in Palo Alto (17 mi)
Overseen byRichard W Childs, M.D.
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Disqualifiers: HIV, Pregnancy, Fanconi anemia, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Background:
Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective.
Objective:
To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective.
Eligibility:
Recipients ages 4-60 with SAA or MDS
Donors ages 4-75
Design:
Recipients will be screened with:
* Blood, lung, and heart tests
* Bone marrow biopsy
* CT scan
Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose.
Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits:
* First 3-4 months: 1-2 times weekly
* Then every 6 months for 5 years
Donors will be screened with:
* Physical exam
* Medical history
* Blood tests
Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein.
Donors will get Filgrastim or biosimilar (G-CSF) injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
How is the treatment Omidubicel unique for aplastic anemia and myelodysplastic syndrome?
Omidubicel is unique because it is an ex vivo expanded stem cell product derived from umbilical cord blood, which allows for faster engraftment and fewer infections compared to standard umbilical cord blood transplants. This makes it a promising alternative for patients who lack a matched donor, offering improved immune recovery and reduced infectious complications.
12345Eligibility Criteria
This trial is for people aged 4-60 with severe aplastic anemia or myelodysplastic syndrome (MDS) who haven't responded to standard treatments. They need a matching cord blood unit and must understand the study's nature. Excluded are those with certain heart, kidney, liver conditions, active infections, other cancers within 5 years, specific allergies, HIV positive status or if they're pregnant.Inclusion Criteria
My cord blood unit was processed and stored according to required standards.
My cord blood unit meets specific cell count criteria and has approval from Gamida Cell.
I understand this study is experimental and I (or my guardian) can consent.
+7 more
Exclusion Criteria
HIV positive
Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy, if of childbearing potential for one year
My lung's ability to transfer gas is less than 40% of what's expected.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Multiple visits for blood, lung, heart tests, bone marrow biopsy, and CT scan
Conditioning
Participants receive chemotherapy infusions and a radiation dose to prepare for transplantation
11 days
Inpatient
Transplantation
Participants receive the donor cells through an IV line
1 day
Inpatient
Hospital Stay
Participants remain in the hospital for monitoring and recovery post-transplant
3-4 weeks
Inpatient
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
1-2 times weekly for the first 3-4 months, then every 6 months
Participant Groups
The trial tests a new treatment method using Omidubicel (formerly CordIn), which involves co-infusing stem cells from both a family member and unrelated donor cord blood to improve bone marrow transplant outcomes in patients with SAA or MDS.
1Treatment groups
Experimental Treatment
Group I: 1Experimental Treatment2 Interventions
CordIn is a cryopreserved stem/progenitor cell-based product of purified CD133+ cells composed of ex vivo expanded allogeneic UCB cells.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Heart, Lung, and Blood Institute (NHLBI)Lead Sponsor
References
Multicenter Long-Term Follow-Up of Allogeneic Hematopoietic Cell Transplantation with Omidubicel: A Pooled Analysis of Five Prospective Clinical Trials. [2023]Omidubicel is an umbilical cord blood (UCB)-derived ex vivo-expanded cellular therapy product that has demonstrated faster engraftment and fewer infections compared with unmanipulated UCB in allogeneic hematopoietic cell transplantation. Although the early benefits of omidubicel have been established, long-term outcomes remain unknown. We report on a planned pooled analysis of 5 multicenter clinical trials including 105 patients with hematologic malignancies or sickle cell hemoglobinopathy who underwent omidubicel transplantation at 26 academic transplantation centers worldwide. With a median follow-up of 22 months (range, .3 to 122 months), the 3-year estimated overall survival and disease-free survival were 62.5% and 54.0%, respectively. With up to 10 years of follow-up, omidubicel showed durable trilineage hematopoiesis. Serial quantitative assessments of CD3+, CD4+, CD8+, CD19+, CD116+CD56+, and CD123+ immune subsets revealed median counts remaining within normal ranges through up to 8 years of follow-up. Secondary graft failure occurred in 5 patients (5%) in the first year, with no late cases reported. One case of donor-derived myeloid neoplasm was reported at 40 months post-transplantation. This was also observed in a control arm patient who received only unmanipulated UCB. Overall, omidubicel demonstrated stable trilineage hematopoiesis, immune competence, and graft durability in extended follow-up.
Omidubicel: First Approval. [2023]Omidubicel (omidubicel-onlv; Omisirge®) is a nicotinamide-modified stem cell graft derived from cord blood that is being developed by Gamida Cell for the treatment of haematological malignancies and haemoglobinopathies. In April 2023, omidubicel received its first approval in the USA for use in adults and children aged ≥ 12 years with haematological malignancies who are planned for cord blood transplantation following myeloablative conditioning to reduce the incidence of infection and the time to neutrophil recovery. This article summarizes the milestones in the development of omidubicel leading to this first approval.
Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. [2023]Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P
A new beginning: can omidubicel emerge as the next, viable alternative donor source? [2023]Umbilical cord blood (UCB) transplantation (CBT) has been an important alternative donor option for patients lacking matched related donor (MRD) or unrelated donor (URD) grafts. Only 30% of patients with high-risk hematologic malignancies have a human leukocyte antigen (HLA)-identical sibling; subjects without a MRD option are referred for HLA-matched URD selection, or utilize alternative donor sources such as HLA-mismatched URD, UCB, or haploidentical donor grafts. While CBT demonstrates an excellent graft-versus-leukemia (GVL) effect, use of UCB as a graft source is limited due to a lower cell dose that can result in delayed engraftment and an immature immune system with increased infectious risk as a consequence. Together, increased transplant related mortality (TRM) has been associated with UCB allografts. Omidubicel is an ex vivo expanded single cord blood product that has demonstrated rapid engraftment, improved immune reconstitution, and reduced infectious complications in clinical trials. Omidubicel has now been granted U.S. Food & Drug Administration approval to enhance neutrophil recovery and decrease infectious risk. This review will focus on CBT, benefits and barriers to using this alternative donor source, and finally the potential advancements with incorporation of omidubicel in the transplant setting for malignant and non-malignant diseases.
Lymphoid and myeloid immune cell reconstitution after nicotinamide-expanded cord blood transplantation. [2023]Omidubicel (nicotinamide-expanded cord blood) is a potential alternative source for allogeneic hematopoietic cell transplantation (HCT) when an HLA-identical donor is lacking. A phase I/II trial with standalone omidubicel HCT showed rapid and robust neutrophil and platelet engraftment. In this study, we evaluated the immune reconstitution (IR) of patients receiving omidubicel grafts during the first 6 months post-transplant, as IR is critical for favorable outcomes of the procedure. Data was collected from the omidubicel phase I-II international, multicenter trial. The primary endpoint was the probability of achieving adequate CD4+ T-cell IR (CD4IR: > 50 × 106/L within 100 days). Secondary endpoints were the recovery of T-cells, natural killer (NK)-cells, B-cells, dendritic cells (DC), and monocytes as determined with multicolor flow cytometry. LOESS-regression curves and cumulative incidence plots were used for data description. Thirty-six omidubicel recipients (median 44; 13-63 years) were included, and IR data was available from 28 recipients. Of these patients, 90% achieved adequate CD4IR. Overall, IR was complete and consisted of T-cell, monocyte, DC, and notably fast NK- and B-cell reconstitution, compared to conventional grafts. Our data show that transplantation of adolescent and adult patients with omidubicel results in full and broad IR, which is comparable with IR after HCT with conventional graft sources.