Personalized rATG for Leukemia

Overseen By Michael Scordo, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active disease, Uncontrolled infection, HIV, 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

59 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to see if conditioning regimens that include personalized rabbit ATG (P-rATG) help the immune system recover sooner and decrease the chances of transplant-related side effects. Participants in this study will be children and adults who have acute leukemia or myelodysplastic syndrome (MDS), and will receive a standard conditioning regimen to prepare the body for an allogeneic hematopoietic cell transplant (allo-HCT). The conditioning regimen will include r-ATG, one of two combinations of chemotherapy, and possibly total body irradiation (TBI).

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.

How is the treatment Personalized rATG (P-rATG) different from other leukemia treatments?

Personalized rATG (P-rATG) is unique because it is tailored to the individual genetic makeup of a patient's leukemia, potentially targeting specific genetic alterations that drive the cancer. This personalized approach aims to improve treatment effectiveness by focusing on the unique characteristics of each patient's disease, unlike standard treatments that may not account for individual genetic differences. ^{1 2 3 4 5}

Research Team

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for children and adults with acute leukemia or myelodysplastic syndrome (MDS) who are preparing for their first bone marrow transplant. Participants must have certain levels of disease remission, normal organ function, and be able to tolerate cytoreduction. Pregnant or breastfeeding women, those with active brain cancer or uncontrolled infections, HIV/HTLV-positive individuals, and previous transplant recipients cannot join.

Inclusion Criteria

I am between 2 and 12 years old.

My organs are functioning well.

1 week 40.6 + / - 14.8

Exclusion Criteria

Patient seropositivity for HIV I/II and/or HTLV I/II.

Patients unwilling to use contraception during the study period.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive a conditioning regimen including P-rATG, chemotherapy, and possibly total body irradiation to prepare for allo-HCT

12 days

Daily visits for treatment administration

Hematopoietic Cell Transplant (HCT)

Participants undergo the allogeneic hematopoietic cell transplant

1 day

Inpatient procedure

Follow-up

Participants are monitored for immune reconstitution and overall survival

100 days

Regular follow-up visits

Long-term Follow-up

Participants are monitored for overall survival and long-term outcomes

2 years

Treatment Details

Interventions

• Personalized rATG (P-rATG)

Trial Overview The study tests if a personalized rabbit Anti-thymocyte Globulin (rATG) in the conditioning regimen before a bone marrow transplant can improve immune recovery and reduce side effects. Patients will receive rATG along with chemotherapy combinations and possibly total body irradiation.

Participant Groups

Group I: P-rATG with total body irradiation, thiotepa, cyclophosphamide Experimental Treatment 5 Interventions

P-rATG days (always starting on Day -12 to -10) * Hyper fractionated total body irradiation (1375 - 1500cGy\*) Day -9 to -6 * Thiotepa (5mg/kg/day x 2 day) Day -5 to -4 * Cyclophosphamide (60mg/kg/day x 2 days) Day -3 to -2 * GCSF Day +7 \*TBI dose in 125cGy fractions (with lung shielding) and total dose to be determined by treating physician/radiation oncology and is based off age, stage of disease, and anesthesia requirements.

Group II: P-rATG with busulfan, melphalan and fludarabine Experimental Treatment 5 Interventions

P-rATG days (Appendix A - always starting on Day -12 to -10) * Busulfan -Day -9 to -7 * Initial dose per table in Appendix B; doses 2-3 to be adjusted per PK for target cumulative exposure of 65 mg\*h/L Melphalan (70mg/m2/day x 2 days) Day -6 to -5 * Fludarabine (25mg/m2/day x 5 days) Day -6 to -2 * GCSF Day +7

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Monovalent FLT3-targeted CAR T cells (FLT3CART) and bispecific CD19xFLT3CART show strong anti-leukemia activity in preclinical models of FLT3-mutant acute myeloid leukemia (AML) and KMT2A-rearranged acute lymphoblastic leukemia (ALL), indicating their potential as effective treatments.

These CAR T-cell therapies demonstrated minimal cross-reactivity with normal tissues and significant in vivo inhibition of leukemia proliferation, suggesting a promising safety profile and efficacy for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3- mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia. Niswander, LM., Graff, ZT., Chien, CD., et al.[2023]

References

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

In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets. [2021]

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

Fine-tuning patient-derived xenograft models for precision medicine approaches in leukemia. [2018]

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

Intratumoral Heterogeneity: Tools to Understand and Exploit Clone Wars in AML. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3- mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia. [2023]