PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation

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).

Study Overview

• Status: Completed
• Conditions: Lymphoma; Myelodysplastic Syndromes; Acute Leukemia; Myeloproliferative Neoplasm
• Intervention / Treatment: Drug: VIC- 1911

Detailed Description

Determination of the optimal dose during the Phase I trial is based on Dose Limiting Toxicity for safety and reduction of CD4+, pH3ser10+ T cells (phosphorylated histone 3 serine 10 is a biomarker of Aurora kinase A activity) for efficacy. Phase II will be powered to improve grade III-IV acute graft-versus-host disease and relapse after alloHCT, compared to historical estimates at the University of Minnesota.

Patients will receive myeloablative conditioning (MAC) with total body irradiation (TBI) followed by infusion of HLA-matched related or unrelated peripheral blood stem cells (PBSC) on day 0. Cyclophosphamide will be administered on days +3 and +4. Sirolimus targeting 8-12ng/ml will begin on day +5 until day +365. VIC-1911 will be administered as 25 mg, 50 mg, or 75 mg orally BID from day +5 to day +45 according to the rules of our phase I study. The lowest biologically active and safe dose of VIC-1911 will be identified as the recommended phase II dose.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of

  • acute leukemia in complete remission, or
  • myelodysplasia with <5% blasts, or
  • myeloproliferative neoplasm/myelofibrosis with <5% marrow or circulating blasts
  • chemosensitive Hodgkin or non-Hodgkin lymphoma
• Age 18 years or older
• Performance status of ≥ 80% Karnofsky

• Adequate organ function within 28 days of study registration defined as:

  • left ventricular ejection fraction ≥ 45%
  • pulmonary function with FEV1, FVC, and DLCO ≥ 50% predicted
  • AST and ALT < 2 times upper limit of normal
  • Total bilirubin <1.5 times the upper limit of normal. If the patient is suspected of having Gilbert syndrome, they require prior approval of the medical monitor
  • creatinine clearance ≥ 50cc/min
  • no active/uncontrolled infection
  • negative HIV, HBV and HCV
  • ferritin < 2000 ng/ml
• Patients able to tolerate oral medication
• Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment through 60 days after the last treatment of VIC-1911 or sirolimus
• Able to provide written voluntary consent prior to the performance of any research related tests or procedures

Exclusion Criteria:

• HCT-CI > 4 or unable to receive myeloablative TBI

• Use of planned post-transplant maintenance therapy to begin prior to day +75. Patients may receive standard of care maintenance therapies starting at day

  +75 or later

• Patients with a history of hypersensitivity to any of the investigational products

• Pregnant or breastfeeding as agents used in this study are Pregnancy Category

  o C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, and Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 28 days of study registration.

• Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 60 days after the last treatment of VIC-1911 or sirolimus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PTCy/sirolimus plus VIC-1911; Patients enrolled and treated with PTCy/sirolimus plus VIC-1911	Drug: VIC- 1911; 25 mg, 50 mg, or 75 mg administered twice a day from day 5 post HCT to day 45, and the dose escalation will stop once we identify the lowest biologically active and safe dose of VIC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Optimal Dose of VIC-1911 When Given in Combination With Standard Immunosuppressive Therapy in Adult Patients Undergoing Myeloablative Stem Cell Transplantation.	The optimal dose will be identified using the EffTox design. The proportion of patients with an average CD4+, pH3ser10+ T cell of <54%. The minimum desired biologic efficacy is 65% of patients by day 21 (+/- 3 days) with <30% of patients experiencing a DLT. Data only to reported from arm with maximum tolerated dose.	21 days post treatment
Progression-free Survival	Participant progression-free survival assessed using aGVHD data.	1 Year
Relapsed Assessment (Phase I)	Assessment to determine if patient has relapse in MTD arm. Data only to reported from arm with maximum tolerated dose.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival for participants on MTD arm. Data only to reported from arm with maximum tolerated dose.	1 year
To Determine the Cumulative Incidences of Acute GVHD	Assessment of aGVHD for MTD arm. Data only to reported from arm with maximum tolerated dose.	Day 100
To Determine the Cumulative Incidences of Chronic GVHD	Assessment of cGVHD	12 months
Progression-free Survival Comparing Graft-Versus-Host Disease-Free (GRFS) to the Standard PTCY Plus Tacrolimus/Mycophenolate Mofetil Regimen From MT2015-29	Progression-free Survival assessed using GRFS defined as grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, relapse, or death by 1 year	12 months
Progression Free Survival	Percentage of participants with progression free survival at 1 year for MTD arm. Data only to reported from arm with maximum tolerated dose.	1 Year
Frequency of CMV Reactivation and Disease	Analyze the frequency of CMV reactivation and disease for MTD arm. Data only to reported from arm with maximum tolerated dose.	Day 100

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Sherman Holtan, MD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): June 30, 2025

Study Registration Dates

• First Submitted: November 3, 2021
• First Submitted That Met QC Criteria: November 3, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Estimated): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Allogeneic; Myeloablative; VIC-1911; PTCy
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Lymphoma; Myelodysplastic Syndromes; Myeloproliferative Disorders
• Other Study ID Numbers: 2021LS006; MT2021-01 (Other Identifier: University of Minnesota)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No