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

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ClinicalTrials.gov Identifier: NCT05120570
Recruitment Status : Recruiting
First Posted : November 15, 2021
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Acute Leukemia Myelodysplastic Syndromes Myeloproliferative Neoplasm Lymphoma Drug: VIC- 1911 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation
Actual Study Start Date : March 17, 2022
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : March 31, 2028


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.




Primary Outcome Measures :
  1. Determine the optimal dose of VIC-1911 when given in combination with standard immunosuppressive therapy in adult patients undergoing myeloablative stem cell transplantation. [ Time Frame: 21 days post treatment ]
    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.

  2. Confirm safety and obtain an estimate of long-term efficacy as measured by aGVHD assessed (Phase II) [ Time Frame: Day 100 ]
    Assessment for aGVHD

  3. Relapsed assessment (Phase II) [ Time Frame: 12 months ]
    Assessment to determine if patient has relapse


Secondary Outcome Measures :
  1. Analyze markers of mTOR and IL-2 activity cells [ Time Frame: Pre-condition, before Day 1 (Day 0) ]
    Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells

  2. Analyze markers of mTOR and IL-2 activity cells [ Time Frame: Day 21 ]
    Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells

  3. Analyze markers of mTOR and IL-2 activity cells [ Time Frame: Day 100 ]
    Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells

  4. To determine the cumulative incidences of acute GVHD [ Time Frame: Day 100 ]
    Assessment of aGVHD

  5. To determine the cumulative incidences of chronic GVHD [ Time Frame: 12 months ]
    Assessment of cGVHD

  6. Compare Graft-Versus-Host Disease-Free (GRFS) to the standard PTCY plus tacrolimus/mycophenolate mofetil regimen from MT2015-29 [ Time Frame: 12 months ]
    GRFS defined as grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, relapse, or death by 1 year

  7. Compare duration of initial transplant hospitalization to patients age 18+ who received treatment on MT2015-29 [ Time Frame: 12 months ]
    Comparison hospitalization days with another trial's data (MT2015-29)

  8. To measure Quality of life [ Time Frame: Through day 100 ]
    Use quality of life questionnaire to measure patients' quality of life.

  9. To analyze the frequency of CMV reactivation and disease [ Time Frame: Through day 180 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05120570


Contacts
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Contact: Cancer Center Clinical Trials Office 612 624 2620 ccinfo@umn.edu

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Sherman Holtan, MD Masonic Cancer Center, University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT05120570    
Other Study ID Numbers: 2021LS006
MT2021-01 ( Other Identifier: University of Minnesota )
First Posted: November 15, 2021    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
VIC-1911
PTCy
Myeloablative
Allogeneic
Additional relevant MeSH terms:
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Myelodysplastic Syndromes
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases