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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a personalized treatment approach using rATG (rabbit anti-thymocyte globulin) to help the immune system recover faster and reduce transplant side effects for individuals undergoing a bone marrow transplant. The focus is on patients with acute leukemia or myelodysplastic syndrome (MDS), who will receive a tailored conditioning regimen with rATG, chemotherapy, and possibly total body irradiation to prepare for the transplant. Suitable candidates include those with acute leukemia or MDS who can undergo this type of treatment and have specific risk features. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from innovative therapies.

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 trial's treatments are likely to be safe?

Research has shown that personalized rabbit ATG (P-rATG) is being studied to improve recovery after a bone marrow transplant. Previous studies found that lower doses of rabbit ATG after a transplant can reduce the risk of dying from the transplant itself, rather than the disease, by 3-4 times compared to higher doses. Adjusting the dose of P-rATG can thus make the procedure safer for patients.

For those receiving P-rATG with total body irradiation, thiotepa, and cyclophosphamide, the safety results are similar. When combined with busulfan, melphalan, and fludarabine, the safety findings also support careful dosing to lower risks. These studies demonstrate that when P-rATG is dosed correctly, it is well-tolerated and can be an important part of transplant care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Personalized rATG (P-rATG) for leukemia because it offers a tailored approach, potentially increasing the effectiveness of treatment. Unlike standard options, P-rATG is customized based on individual patient factors, which could lead to better outcomes. Additionally, it is combined with intensive conditioning regimens like total body irradiation or other chemotherapeutic agents such as busulfan and melphalan, which are strategically sequenced to optimize their impact against leukemia cells. This personalized protocol aims to enhance the body's ability to fight the cancer more efficiently than current generalized treatments.

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

Research has shown that personalized rabbit anti-thymocyte globulin (P-rATG) can help the immune system recover faster after a transplant. Studies have found that using rabbit ATG in preparation for a transplant lowers the risk of complications related to the procedure. Specifically, a low dose of rATG after a transplant reduces the chance of dying from causes other than cancer returning by three to four times compared to higher doses. In this trial, participants will receive P-rATG in combination with either total body irradiation, thiotepa, and cyclophosphamide, or with busulfan, melphalan, and fludarabine. This treatment is under study for its potential to improve outcomes in patients receiving donor stem cell transplants for conditions like acute leukemia and myelodysplastic syndrome (MDS). These promising results suggest that P-rATG could be effective in these situations. ^{1 2 3 4 6}

Who Is on the Research Team?

Kevin Curran

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04872595?cond=Myelodysplastic+syndromes&aggFilters=studyType%3Aint

Study Details | NCT04872595 | A Modified Dose of Rabbit ... 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 ...

2. withpower.com withpower.com/trial/phase-3-leukemia-myeloid-acute-3-2021-9eea9

Personalized rATG for Leukemia · Info for Participants 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18560

Outcomes of split-dose lymphocyte-adjusted rabbit ATG in ... Methods: This retrospective, single-center review evaluated patients who received an allogeneic stem cell transplant from any donor type with ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324924000227

Impact of rabbit anti-thymocyte globulin (ATG) exposure on ... Exposure of rATG post-HCT can affect outcomes: overexposure leads to an increased risk of NRM due to poor CD4+IR, and underexposure leads to an increased risk ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10997457/

Impact of Rabbit Anti-Thymocyte Globulin (ATG) Exposure ... A low post-HCT rATG exposure was associated with 3-4-fold lower risk of NRM compared to the 2 higher exposure groups.

6. astctjournal.org astctjournal.org/article/S2666-6367(24)00556-6/fulltext

Patients Beyond the Optimal Range of rATG-AUC Still ... This study compared the outcomes of the optimal AUC arm with nonoptimal AUC arm to assess the effect of the rATG-targeted dosing strategy.