Stem Cell Transplantation for Leukemia

Not currently recruiting at 69 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Oncology Group

Disqualifiers: Genetic disorders, Pregnancy, Uncontrolled infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best source for stem cell transplants in young people with acute leukemia or myelodysplastic syndrome (MDS). It compares stem cell transplants from a partially matched family donor (haploidentical hematopoietic cell transplantation, or haploHCT) to those from an unrelated donor (matched unrelated donor hematopoietic cell transplantation, or MUD-HCT). The goal is to determine which option more effectively restores healthy blood cell production after intense cancer treatment. This trial may suit children, adolescents, and young adults diagnosed with high-risk leukemia or MDS who lack a fully matched sibling donor. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves high doses of chemotherapy and/or radiation therapy, it's possible that some medications may need to be adjusted or paused. Please consult with the trial coordinators or your healthcare provider for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both haploidentical hematopoietic cell transplantation (haploHCT) and matched unrelated donor hematopoietic cell transplantation (MUD-HCT) are generally safe for treating leukemia and myelodysplastic syndrome (MDS).

For haploHCT, studies have found it to be well-tolerated, with some patients experiencing less chronic graft-versus-host disease (GVHD) compared to other transplant types. In one study, combining haploHCT with umbilical cord blood infusion helped patients recover blood cell production quickly and safely.

For MUD-HCT, research indicates it is as safe as transplants from matched sibling donors, suggesting similar outcomes for patients. Additionally, MUD transplants using specific GVHD prevention strategies have shown good results with manageable side effects.

Both options aim to provide effective treatment with manageable risks, offering hope for patients needing stem cell transplants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these leukemia treatments because they explore innovative approaches to stem cell transplantation. Haploidentical hematopoietic cell transplantation (haploHCT) offers a unique solution by using partially matched family donors, making it accessible to more patients who can't find a perfect match. This method often incorporates post-transplant cyclophosphamide (PTCy) or alpha beta T cell depletion to reduce the risk of graft-versus-host disease (GVHD), which is a common complication in transplants. Meanwhile, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) uses a conditioning regimen that can be tailored to the patient, potentially increasing the treatment's effectiveness and safety. These strategies are distinct from traditional treatments that rely on fully matched sibling donors and standard conditioning protocols, which can limit patient eligibility and carry higher risks of complications.

What evidence suggests that this trial's treatments could be effective for leukemia?

Research has shown that both haploidentical hematopoietic cell transplantation (haploHCT) and matched unrelated donor hematopoietic cell transplantation (MUD-HCT) offer similar survival outcomes for patients with acute leukemia. In this trial, participants will be assigned to different arms to receive either haploHCT or MUD-HCT. Studies have found that haploHCT and MUD-HCT can lead to comparable overall survival rates. Patients who undergo haploHCT often experience results similar to those who undergo MUD-HCT. Some research even suggests that certain haploHCT groups might achieve the best survival rates. For MUD-HCT, survival times often match those from related donors, making it a good option for patients without a perfect donor match. Both types of transplants aim to restore healthy blood cell production after intensive chemotherapy or radiation. ^{6 7 8 9 10}

Who Is on the Research Team?

Heather J Symons

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults aged 6 months to under 22 years with acute leukemia or myelodysplastic syndrome (MDS) who need a stem cell transplant but don't have a matched sibling donor. Participants must be in good health with proper kidney, liver, heart, and lung function. They can't join if they're pregnant, unwilling to use contraception during the study, have uncontrolled infections or certain genetic disorders.

Inclusion Criteria

I have a perfectly matched donor for my treatment.

I am diagnosed with a blood cancer and need a stem cell transplant.

I have a family member who is a partial match for a stem cell donation.

Exclusion Criteria

I do not have any health issues that would prevent me from undergoing a bone marrow transplant.

I am currently pregnant.

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Conditioning

Patients receive a myeloablative conditioning regimen with either TBI-based or chemotherapy-based treatment

7-8 days

Daily visits for treatment

Transplantation

Patients undergo hematopoietic cell transplantation (HCT) with either haploidentical or matched unrelated donor cells

1 day

1 visit (in-patient)

Post-Transplantation Monitoring

Patients receive GVHD prophylaxis and are monitored for engraftment and complications

100 days

Frequent visits for monitoring and treatment

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes

Up to 5 years

Periodic visits

What Are the Treatments Tested in This Trial?

Interventions

• Haploidentical hematopoietic cell transplantation (haploHCT)
• matched unrelated donor hematopoietic cell transplantation (MUD-HCT)

Trial Overview The trial compares two types of stem cell transplants: one from mismatched related donors (family members not fully matching) versus another from matched unrelated donors found through registries. It aims to determine which source is better for treating high-risk leukemia or MDS after receiving intensive chemotherapy or radiation therapy.

How Is the Trial Designed?

Group I: Arm C (haploHCT) Experimental Treatment 20 Interventions

Patients who only have a haplo donor receive a myeloablative conditioning regimen with PTCy or alpha beta T cell depletion at the discretion of the treating provider. Patients then undergo haploHCT on day 0. Patients undergoing myeloablative conditioning regimen with PTCy also receive GVHD prophylaxis on days 3-5. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.

Group II: Arm B (MUD-HCT) Experimental Treatment 17 Interventions

Patients receive a TBI-based or chemotherapy-based myeloablative conditioning regimen between days -9 and -2, followed by MUD-HCT on day 0. Patients then receive GVHD prophylaxis regimen on days 1-11. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.

Group III: Arm A (halploHCT) Experimental Treatment 20 Interventions

Patients receive a myeloablative conditioning regimen with PTCy or alpha beta T cell depletion at the discretion of the treating provider. Patients then undergo haploHCT on day 0. Patients undergoing myeloablative conditioning regimen with PTCy also receive GVHD prophylaxis on days 3-5. Patients undergo lumbar puncture, bone marrow aspiration, and ECHO or MUGA during screening. Patients also undergo collection of blood throughout the trial.

Haploidentical hematopoietic cell transplantation (haploHCT) is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Haploidentical stem cell transplantation for:

• Acute leukemia
• Myelodysplastic syndrome
• Hematologic malignancies

Approved in United States as Haploidentical hematopoietic cell transplantation for:

• Acute leukemia
• Myelodysplastic syndrome
• Blood cancers

Approved in Canada as Haploidentical stem cell transplantation for:

• Acute leukemia
• Myelodysplastic syndrome
• Hematologic malignancies

Approved in Japan as Haploidentical hematopoietic cell transplantation for:

• Acute leukemia
• Myelodysplastic syndrome
• Blood cancers

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Published Research Related to This Trial

Patients with acute leukemia in remission have significantly better outcomes when receiving allogeneic stem cell transplants (allo-SCT) from fully matched unrelated donors (MUD 10/10) compared to haploidentical donors (Haplo).

There is no significant difference in outcomes between transplants from haploidentical donors and mismatched unrelated donors (MMUD 9/10), indicating that both can be viable options when a fully matched donor is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. Piemontese, S., Ciceri, F., Labopin, M., et al.[2018]

Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) shows comparable overall survival and progression-free survival rates to matched unrelated donor transplantation (MUD-SCT), based on a meta-analysis of 17 studies.

Haplo-SCT significantly reduces the risk of acute and chronic graft-versus-host disease compared to MUD-SCT, making it a safer option for patients needing urgent transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation vs matched unrelated donor transplantation in adults with hematologic malignancies: a systematic review and meta-analysis. Ma, L., Han, X., Jiang, S., et al.[2021]

A study comparing 52 patients with acute myeloid leukemia (AML) who received haploidentical transplants using peripheral blood to 88 patients who received HLA-matched unrelated donor (MUD) transplants found similar overall outcomes between the two groups.

However, patients receiving haploidentical transplants experienced slower recovery of blood cell counts, particularly for platelets and neutrophils, indicating a potential difference in post-transplant recovery dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Outcomes after Peripheral Blood Haploidentical versus Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia: A Retrospective Single-Center Review. Rashidi, A., DiPersio, JF., Westervelt, P., et al.[2018]

In a study of 2223 adult patients with acute myelogenous leukemia, those receiving hematopoietic cell transplants (HCT) from matched related donors (MRD) experienced significantly lower rates of acute graft-versus-host disease (GVHD) compared to those receiving transplants from matched unrelated donors (MUD).

While early mortality was higher in patients receiving transplants from 7/8 MUD donors compared to MRD donors, overall survival rates beyond 6 months were similar for both MRD and 8/8 MUD recipients, indicating comparable long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Saber, W., Opie, S., Rizzo, JD., et al.[2022]

Haploidentical stem cell transplantation (haplo-SCT) is a viable option for high-risk leukemia patients without matched donors, showing comparable outcomes to other transplantation methods like matched sibling donor and umbilical cord blood transplants.

Innovative strategies, such as co-transplanting haploidentical allografts with cord blood, have demonstrated feasibility and potential to enhance treatment effectiveness by reducing relapse rates after haplo-SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for the treatment of leukemia: current status. Chang, YJ., Wang, Y., Huang, XJ.[2014]

The study found that the costs associated with allogeneic hematopoietic stem cell transplantation (HSCT) using matched unrelated donors (MUD) and haploidentical donors are similar, with total costs around €115,724 for MUD and €113,312 for haploidentical donors.

Pre-transplant costs were significantly higher for MUD HSCT (€35,222) compared to matched related (€15,356) and haploidentical HSCT (€16,097), indicating that while initial costs differ, overall expenses balance out, suggesting donor choice may depend more on availability and logistics rather than cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of donor type on resource utilisation and costs in allogeneic haematopoietic stem cell transplantation in the Netherlands. van Gorkom, G., Van Elssen, C., Janssen, I., et al.[2022]

Haploidentical hematopoietic stem cell transplantation (HSCT) has become a viable option for patients with acute leukemia who cannot find a well-matched donor, addressing the issue that 25% to 60% of patients may not find an 8/8 HLA-matched unrelated donor.

New techniques in T-cell depletion and immunotherapy are enhancing the safety and efficacy of haploidentical HSCT, making it crucial for physicians to evaluate all donor options based on individual patient needs and circumstances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplant outcomes in acute leukemia. II. Hough, R., Rocha, V.[2021]

In patients undergoing haplotype-mismatched CD34(+) selected allogeneic stem cell transplantation (HASCT) for acute myeloid leukemia, the reconstituted NK cells showed a significantly altered phenotype, with reduced effector CD56(dim) cells and lower expression of key antileukemia molecules like perforin and Fas-ligand.

To enhance NK cell function and potentially improve clinical outcomes, subsequent patients received donor NK cell infusions along with interleukin-2, which successfully increased perforin and Fas-L expression and boosted NK cell cytotoxicity in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered phenotype of natural killer cell subsets after haploidentical stem cell transplantation. Schulze, A., Schirutschke, H., Oelschlägel, U., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12037578/

Haploidentical, matched-related, and matched-unrelated ... This study is the first in a developing country to use the CIBMTR's resources and expertise to analyze local hematopoietic cell transplant ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11006712/

Haploidentical and matched unrelated donor allogeneic ... Haploidentical and matched unrelated donor allogeneic hematopoietic stem cell transplantation offer similar survival outcomes for acute leukemia.

3. nature.com nature.com/articles/s41409-025-02708-w.pdf

Haploidentical versus matched unrelated donor ... Molecular disparity in human leukocyte antigens is associated with outcomes in haploidentical stem cell transplantation. Blood Adv. 2020;4 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724005281

Haploidentical Versus Mismatched Unrelated Donor ... Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.70069

American Journal of Hematology | Blood Research Journal Previous studies have suggested that haploidentical hematopoietic cell transplantation (Haplo-HCT) has comparable outcomes to MUD-HCT or even to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345264/

Outcomes of haploidentical vs mismatched unrelated ... Key Points. •. Donor age was a more consistently influential factor as a main effect, with a nonlinear relationship with overall mortality hazard.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05457556

Study Details | NCT05457556 | Mismatched Related Donor ... This phase III trial compares hematopoietic (stem) cell transplantation (HCT) using mismatched related donors (haploidentical [haplo]) versus matched unrelated ...

8. ashpublications.org ashpublications.org/bloodadvances/article/3/12/1826/261334/Outcomes-of-haploidentical-vs-matched-sibling

Outcomes of haploidentical vs matched sibling transplantation ... Key Points. PT-Cy–based Haplo-HCT resulted in less chronic GVHD compared to matched sibling transplantation in patients with AML in CR1.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725013752

Haploidentical hematopoietic cell transplantation ... Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising treatment option for T-cell acute lymphoblastic leukemia (T-ALL). Co- ...

10. astctjournal.org astctjournal.org/article/S2666-6367(25)01408-3/fulltext

Efficacy and Safety of Haploidentical Hematopoietic Stem ... Haplo-HSCT combined with UCB infusion is a safe and effective strategy for patients lacking young donors, offering rapid hematopoietic recovery, ...