Haploidentical Transplant for Leukemia

Recruiting 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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II, open-label, non-randomized, prospective study of haploidentical transplantation using KIR-favorable donors for children with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). The relationship of KIR2DL1 polymorphisms to survival in children with these diseases undergoing any approach to allogeneic HCT during the study time frame will also be determined.

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.

What data supports the effectiveness of the treatment KIR Favorable Mismatched Haplo Transplant for leukemia?

Research shows that haploidentical stem cell transplants, which involve mismatched donor cells, can be effective for high-risk leukemia patients who lack matched donors. The treatment uses natural killer (NK) cells from the donor to help fight leukemia, and studies have found it can lead to good survival rates and low relapse rates. ^{1 2 3 4 5}

Is haploidentical transplant generally safe for humans?

Haploidentical transplants, which involve using a partially matched donor, have been studied for safety and show promising outcomes in terms of survival and relapse rates, especially when specific genetic factors are considered. However, there can be risks such as graft-versus-host disease (a condition where the donor's immune cells attack the recipient's body), which need to be managed carefully. ^{1 3 6 7 8}

How is the KIR Favorable Mismatched Haplo Transplant treatment different from other leukemia treatments?

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 KIR ligands, enhancing the anti-leukemia effect. This approach can be used when a fully matched donor is unavailable, and it leverages the body's immune response to target leukemia cells more effectively. ^{1 2 3 9 10}

Research Team

Michael Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Eligibility Criteria

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

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

I am younger than 22 years old.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for the treatment of leukemia: current status. [2014]

3. United States pubmed.ncbi.nlm.nih.gov

Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: how NK cells make the difference. [2009]

4. Germany pubmed.ncbi.nlm.nih.gov

Transplantation of haploidentically mismatched stem cells for the treatment of malignant diseases. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic stem cell transplantation with a megadose T-cell-depleted graft: harnessing natural and adaptive immunity. [2012]

6. China pubmed.ncbi.nlm.nih.gov

Impact of incompatible killer cell immunoglobulin-like receptor and its ligand on the outcome of haploidentical bone marrow transplantation. [2016]

7. United States pubmed.ncbi.nlm.nih.gov

Donor KIR2DS1-Mediated Decreased Relapse and Improved Survival Depending on Remission Status at HLA-Haploidentical Transplantation with Post-Transplantation Cyclophosphamide. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Killer Cell Immunoglobulin-Like Receptor-Ligand Mismatch in Donor versus Recipient Direction Provides Better Graft-versus-Tumor Effect in Patients with Hematologic Malignancies Undergoing Allogeneic T Cell-Replete Haploidentical Transplantation Followed by Post-Transplant Cyclophosphamide. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of a pilot study using a chemotherapy-alone protocol for killer Ig-like receptor-ligand-mismatched haploidentical haematopoietic SCT. [2011]