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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination to prevent complications after a bone marrow transplant for individuals with certain blood cancers. It uses VIC-1911, an experimental drug, alongside other medications to reduce the risk of graft-versus-host disease (GVHD), which occurs when transplanted cells attack the body. Individuals who have recently undergone a bone marrow transplant and are in remission from acute leukemia, or have specific other blood conditions, may qualify for this trial. Participants must be able to take oral medication and have no active infections. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that using sirolimus with post-transplant cyclophosphamide (PTCy) is safe and reduces complications after a transplant. This provides insight into the safety of adding VIC-1911 to the treatment.

Early studies with VIC-1911 are encouraging. Patients have shown positive outcomes without severe side effects that would necessitate stopping or lowering the dose. This indicates that VIC-1911 is well-tolerated at the doses tested.

As this study is still in the early stages, more information will emerge as research progresses. However, based on current data, the treatment appears safe for individuals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for acute leukemia, which often involves chemotherapy and radiation, VIC-1911 works differently by specifically targeting cancer cell growth at a molecular level. Researchers are excited about this treatment because it combines PTCy and sirolimus with VIC-1911, potentially offering a more tailored approach to post-transplant care. This combination therapy aims to reduce transplant-related complications and improve patient outcomes by leveraging the unique properties of VIC-1911 to potentially enhance the immune system's ability to fight residual cancer cells.

What evidence suggests that PTCy/sirolimus plus VIC-1911 is effective for preventing GVHD and relapse after alloHCT?

Research has shown that using sirolimus with post-transplant cyclophosphamide (PTCy) reduces complications after a transplant. In this trial, participants will receive a combination of PTCy, sirolimus, and VIC-1911. VIC-1911 blocks AURKA, which is crucial for cancer cell growth. Earlier studies demonstrated positive results with this combination, suggesting it might help prevent cancer recurrence and reduce post-transplant issues. Specifically, the likelihood of remaining leukemia-free has significantly improved, indicating this method's potential effectiveness. Overall, this treatment combination appears promising for enhancing outcomes in people with acute leukemia after a transplant. ^{2 3 6 7 8}

Who Is on the Research Team?

Sherman Holtan, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. withpower.com withpower.com/trial/phase-2-myeloproliferative-disorders-1-2022-119ad

PTCy + Sirolimus/VIC-1911 for Acute Leukemia Post ... The combination of sirolimus and post-transplant cyclophosphamide (PTCy) has been shown to be safe and effective in reducing transplant-related complications ...

2. astctjournal.org astctjournal.org/article/S2666-6367(23)02099-7/pdf

Phase I Trial in Combination with Ptcy/Sirolimu The optimal VIC-1911 dose is 75 mg BID, sup- pressing AURKA activity below the set target (Figure 2C). Engraftment data and patient outcomes appear favorable,.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11993932/

Improved post‐transplant outcomes since 2000 for Ph‐ ... Correspondingly, 3‐year leukemia‐free survival (LFS) improved from 34% to 64%, and overall survival (OS) from 47% to 75% (p < 0.001 for both).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2814074/

Transplant Outcomes in Acute Leukemia (I) - PMC The data support similar leukemia-free survival after transplantation of HLA-matched and 1 or 2 HLA-mismatched UCB and HLA-matched unrelated donor bone marrow.

5. sciencedirect.com sciencedirect.com/science/article/pii/S245231862500008X

Post-transplant cyclophosphamide in matched donor ... OS, disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 55%, 39%, and 15%, respectively. The 2-year CI of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05120570

Study Details | NCT05120570 | PTCy + Sirolimus/VIC-1911 ... This is a single-arm, phase I/II, study of PTCy/sirolimus plus VIC-1911 to prevent GVHD and relapse after Allogeneic Hematopoietic Cell Transplantation (alloHCT) ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123115266

Aurora Kinase a Inhibition for Gvhd and Relapse ... In vitro studies show killing of multiple leukemia cells lines at physiologically achievable VIC-1911 concentrations. VIC 75 mg BID is the ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20109611/

Transplant outcomes in acute leukemia. I - PubMed - NIH In adults with acute leukemia, some reports suggest a survival advantage after transplantation of matched unrelated bone marrow compared to UCB, while others ...