Haploidentical Transplant for Leukemia

Enrolling by invitation at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Michael Pulsipher

Disqualifiers: Pregnancy, HIV, Uncontrolled infections, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for children with certain blood cancers, such as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). The goal is to determine if a specific type of stem cell transplant, known as KIR Favorable Mismatched Haplo Transplant, from a half-matched family donor can improve survival. This study targets children with these specific blood cancers who have not had a previous stem cell transplant and lack a fully matched donor. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the KIR Favorable Mismatched Haplo Transplant has promising safety results. In earlier studies, patients with leukemia who received this treatment had an 88% survival rate over five years, suggesting the treatment is generally well-tolerated.

This method uses special donor cells called natural killer (NK) cells, carefully chosen to match the patient, which helps reduce complications. Although researchers continue to study the treatment, these early findings suggest it might be a safe option for patients.

Overall, available data indicates the treatment is well-tolerated, with no major safety concerns reported so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the KIR Favorable Mismatched Haplo Transplant because it offers a new approach for treating leukemia, specifically in high-risk children with ALL, AML, and MDS. Unlike standard treatments like matched sibling donor transplants or chemotherapy, this method uses a graft that's selectively depleted of certain T cells, which may reduce the risk of complications like graft-versus-host disease. This technique leverages a favorable mismatch in killer-cell immunoglobulin-like receptors (KIR), potentially enhancing the immune system's ability to target and destroy cancer cells. By exploring this innovative immunotherapy strategy, researchers hope to improve disease-free survival rates and offer a more effective treatment option for young patients facing these challenging conditions.

What evidence suggests that KIR Favorable Mismatched Haplo Transplant might be an effective treatment for leukemia?

Research has shown that a new type of transplant, called KIR-favorable mismatched haplo transplants, offers promising results for children with leukemia and myelodysplastic syndrome (MDS). One study found that children who received this transplant had a 79% chance of being disease-free for two years and an 82% chance of overall survival. This is significant because the risk of death from the transplant and the risk of chronic graft-versus-host disease (where the donor's immune cells attack the recipient's body) were both under 10%. These results surpass those from traditional transplants, making this new approach a hopeful option for affected children. Participants in this trial will receive the KIR Favorable Transplant to evaluate its effectiveness in improving disease-free survival one year post-transplant. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for children under 22 with high-risk acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or myelodysplastic syndrome (MDS) who are undergoing a bone marrow transplant. It's open to those eligible for HCT at participating centers and includes patients with specific genetic features or disease statuses outlined in the criteria.

Inclusion Criteria

I am younger than 22 years old.

Does not have a suitable matched or single antigen mismatched related or unrelated donor available at any time

I am mostly independent and can do some daily activities.

Exclusion Criteria

I have a genetic disorder that increases my risk for a certain type of leukemia.

I have HIV or an uncontrolled infection.

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo haploidentical transplantation using KIR-favorable donors with grafts depleted for CD3+ cells

8-12 weeks

Weekly visits for monitoring and treatment adjustments

Follow-up

Participants are monitored for safety, survival, and relapse rates post-transplantation

12 months

Monthly visits for the first year

Open-label extension (optional)

Participants may continue to be monitored for long-term outcomes and survival

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• KIR Favorable Mismatched Haplo Transplant

Trial Overview The study tests haploidentical transplantation using donors with favorable KIR genes in kids with ALL, AML, or MDS. It also examines how variations in the KIR2DL1 gene affect survival post-transplantation. The intervention involves a CliniMacs TCR alpha-beta-Biotin system for T-cell depletion.

How Is the Trial Designed?

Group I: KIR Favorable Transplant Experimental Treatment 1 Intervention

To assess in a multi-center setting whether the disease-free survival (DFS) at one-year post-HCT for children with high-risk ALL, AML and MDS can be improved following favorably KIR-mismatched haplo-HCT using a graft ex vivo depleted of T cell receptor (TCR) αβ+CD3+/CD19+ cells from CliniMacs TCR alpha-beta-Biotin system

Who Is Running the Clinical Trial?

Michael Pulsipher

Lead Sponsor

Trials

1

Recruited

60+

Michael Pulsipher, MD

Lead Sponsor

Trials

5

Recruited

240+

UCSF Benioff Children's Hospital Oakland

Collaborator

Trials

80

Recruited

19,100+

Medical College of Wisconsin

Collaborator

Trials

645

Recruited

1,180,000+

New York Medical College

Collaborator

Trials

73

Recruited

8,700+

Rady Children's Hospital, San Diego

Collaborator

Trials

42

Recruited

14,300+

Ann & Robert H Lurie Children's Hospital of Chicago

Collaborator

Trials

275

Recruited

5,182,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

Haploidentical transplantation from mismatched family donors is a viable option for high-risk acute leukemia patients lacking a matched donor, showing favorable event-free survival compared to other stem cell sources.

The strategy of using high numbers of T-cell-depleted hematopoietic progenitor cells without post-transplant immunosuppression effectively manages graft rejection and graft-versus-host disease, while also emphasizing the importance of natural killer cell activity in preventing leukemia relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity. Aversa, F., Martelli, MF., Velardi, A.[2012]

T-cell-depleted hematopoietic stem cell transplantation (Haplo HSCT) from HLA-haploidentical relatives is an effective treatment for high-risk acute myeloid leukemia (AML) in adults and relapsed acute lymphoblastic leukemia (ALL) in children, as demonstrated by two case studies.

The success of Haplo HSCT is attributed to the anti-leukemia effects of alloreactive NK cells from the donor, and the use of KIR-specific monoclonal antibodies helps identify and quantify these beneficial NK cell subsets, making it easier to select suitable donors and monitor treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference. Locatelli, F., Pende, D., Maccario, R., et al.[2009]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02646839

Study Details | NCT02646839 | KIR Favorable Mismatched ... These results compared favorably with the 5-year survival of 70±38% for transplantations using matched siblings and 61±17% for matched unrelated donors treated ...

2. stanfordhealthcare.org stanfordhealthcare.org/trials/k/NCT02646839.html

KIR Favorable Mismatched Haplo Transplant and ... This is a phase II, open-label, non-randomized, prospective study of haploidentical transplantation using KIR-favorable donors for children with acute ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9918850/

KIR-favorable TCR-αβ/CD19-depleted haploidentical HCT ... Key Points. •. Two-year DFS/OS of children with leukemia/MDS (MRD <0.01%) were 79%/82%, with rates of transplant-related mortality and chronic GVHD <10%.

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02646839/

Clinical Trial: NCT02646839 These results compared favorably with the 5-year survival of 70±38% for transplantations using matched siblings and 61±17% for matched unrelated ...

5. ashpublications.org ashpublications.org/bloodadvances/article/4/4/740/452530/KIR-B-donors-improve-the-outcome-for-AML-patients

KIR B donors improve the outcome for AML patients given ... This analysis combined data from a prospective trial testing URD selection based on KIR genotypes (n = 243) with that from a larger ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2834435/

NKAML: A Pilot Study to Determine the Safety and ... A pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in ...

7. withpower.com withpower.com/trial/phase-3-precursor-cell-lymphoblastic-leukemia-lymphoma-9-2015-73944

Haploidentical Transplant for Leukemia · Info for Participants The KIR Favorable Mismatched Haplo Transplant treatment is unique because it uses a donor's natural killer (NK) cells that are mismatched with the recipient's ...