PTCy + Sirolimus/VIC-1911 for Acute Leukemia Post-transplant Care

Overseen By Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, Hypersensitivity, HCT-CI > 4, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of drugs to prevent complications after a stem cell transplant. It focuses on patients at risk of serious issues like GVHD and relapse. The drugs work together to protect the transplanted cells by suppressing the immune system. Cyclophosphamide combined with tacrolimus has been used to prevent GVHD after a stem cell transplant.

Do I need to stop my current medications for this trial?

The trial information does not specify if 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 drug VIC-1911 for acute leukemia post-transplant care?

The combination of sirolimus and post-transplant cyclophosphamide (PTCy) has been shown to be safe and effective in reducing transplant-related complications like graft-versus-host disease (GvHD) in patients with acute myeloid leukemia (AML), suggesting potential benefits for post-transplant care in acute leukemia. ^{1 2 3 4 5}

Is the combination of PTCy, Sirolimus, and VIC-1911 safe for humans?

Sirolimus, when combined with chemotherapy for acute myeloid leukemia (AML), has been shown to be well-tolerated and safe in humans, with toxicity similar to standard chemotherapy regimens. ^{6 7 8 9 10}

What makes the drug VIC-1911 unique for post-transplant care in acute leukemia?

The treatment combines PTCy (post-transplant cyclophosphamide) with sirolimus and VIC-1911, which may offer a novel approach by targeting specific pathways like mTORC1, potentially enhancing the effectiveness of post-transplant care in acute leukemia compared to traditional chemotherapy alone. ^{5 6 8 9 10}

Research Team

Sherman Holtan, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for adults over 18 with certain blood disorders or lymphoma, who are in remission or have low blast counts. They must have good organ function, not be pregnant or breastfeeding, agree to use contraception, and can't have a high risk of transplant complications (HCT-CI > 4) or hypersensitivity to the drugs used.

Inclusion Criteria

My heart, lungs, liver, and kidneys are functioning well, and I don't have active infections or certain viruses.

I agree to use birth control during and for 60 days after my treatment ends.

My leukemia is in complete remission, or I have a low blast count in myelodysplasia/myelofibrosis, or my lymphoma responds well to chemotherapy.

Exclusion Criteria

I agree to use birth control during and for 60 days after treatment.

I cannot undergo intense bone marrow radiation due to high risk.

Pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Patients receive myeloablative conditioning with total body irradiation followed by infusion of HLA-matched related or unrelated peripheral blood stem cells

1 week

Inpatient stay

Treatment

Cyclophosphamide is administered on days +3 and +4. Sirolimus is administered from day +5 until day +365. VIC-1911 is administered from day +5 to day +45

52 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of acute and chronic GVHD

12 months

Follow-up visits at specified intervals

Treatment Details

Interventions

• VIC-1911

Trial Overview The study tests PTCy/sirolimus combined with VIC-1911 as a way to prevent graft-versus-host disease (GVHD) and relapse after stem cell transplantation from donors. It's an early phase trial where all participants receive the same treatment without comparison groups.

Participant Groups

Group I: PTCy/sirolimus plus VIC-1911 Experimental Treatment 1 Intervention

Patients enrolled and treated with PTCy/sirolimus plus VIC-1911

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

Sirolimus has become a foundational therapy for immunosuppression in transplant patients, significantly reducing the risk of acute allograft rejection by allowing over 80% reduction in calcineurin inhibitor exposure, which leads to better long-term renal function despite some increased risks of lymphoceles and impaired wound healing.

The drug also has anti-cancer properties by inhibiting mTOR, reducing tumor incidence in patients, and is relatively non-nephrotoxic, allowing for the withdrawal of steroid therapy and lower rates of viral infections, making it a promising option in immunosuppressive regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fifteen years of clinical studies and clinical practice in renal transplantation: reviewing outcomes with de novo use of sirolimus in combination with cyclosporine. Kahan, BD.[2014]

In a study of 242 adult patients with acute myeloid leukemia (AML) undergoing their first allogeneic stem cell transplant, the combination of sirolimus and post-transplant cyclophosphamide (Sir-PTCy) was found to be a safe and effective method for preventing graft-versus-host disease (GvHD).

The use of Sir-PTCy resulted in low rates of transplant-related mortality, relapse, and both acute and chronic GvHD across various donor types, indicating its potential as a reliable prophylactic strategy in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia. Lazzari, L., Balaguer-Roselló, A., Montoro, J., et al.[2022]

References

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

Fifteen years of clinical studies and clinical practice in renal transplantation: reviewing outcomes with de novo use of sirolimus in combination with cyclosporine. [2014]

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

Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia. [2022]

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

Calcineurin inhibitor--free graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide and brief-course sirolimus following reduced-intensity peripheral blood stem cell transplantation. [2014]

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

The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Post-remission therapy in acute myeloid leukemia: Are we ready for an individualized approach? [2020]

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

A phase I study of the mammalian target of rapamycin inhibitor sirolimus and MEC chemotherapy in relapsed and refractory acute myelogenous leukemia. [2023]

7. England pubmed.ncbi.nlm.nih.gov

In-vitro synergism of m-TOR inhibitors, statins, and classical chemotherapy: potential implications in acute leukemia. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

A Phase I Trial of Sirolimus with "7&3" Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukemia. [2023]

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

Sirolimus enhances remission induction in patients with high risk acute myeloid leukemia and mTORC1 target inhibition. [2019]

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

FLT3-ITD-, but not BCR/ABL-transformed cells require concurrent Akt/mTor blockage to undergo apoptosis after histone deacetylase inhibitor treatment. [2021]