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

Primary Purpose

Acute Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VIC- 1911
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Acute Leukemia focused on measuring VIC-1911, PTCy, Myeloablative, Allogeneic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center at University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PTCy/sirolimus plus VIC-1911

Arm Description

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

Outcomes

Primary Outcome Measures

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.
Confirm safety and obtain an estimate of long-term efficacy as measured by aGVHD assessed (Phase II)
Assessment for aGVHD
Relapsed assessment (Phase II)
Assessment to determine if patient has relapse

Secondary Outcome Measures

Analyze markers of mTOR and IL-2 activity cells
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
Analyze markers of mTOR and IL-2 activity cells
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
Analyze markers of mTOR and IL-2 activity cells
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
To determine the cumulative incidences of acute GVHD
Assessment of aGVHD
To determine the cumulative incidences of chronic GVHD
Assessment of cGVHD
Compare Graft-Versus-Host Disease-Free (GRFS) to the standard PTCY plus tacrolimus/mycophenolate mofetil regimen from MT2015-29
GRFS defined as grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, relapse, or death by 1 year
Compare duration of initial transplant hospitalization to patients age 18+ who received treatment on MT2015-29
Comparison hospitalization days with another trial's data (MT2015-29)
To measure Quality of life
Use quality of life questionnaire to measure patients' quality of life.
To analyze the frequency of CMV reactivation and disease

Full Information

First Posted
November 3, 2021
Last Updated
April 14, 2023
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT05120570
Brief Title
PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation
Official Title
PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 17, 2022 (Actual)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
March 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemia, Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Lymphoma
Keywords
VIC-1911, PTCy, Myeloablative, Allogeneic

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PTCy/sirolimus plus VIC-1911
Arm Type
Experimental
Arm Description
Patients enrolled and treated with PTCy/sirolimus plus VIC-1911
Intervention Type
Drug
Intervention Name(s)
VIC- 1911
Intervention Description
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 Measure Information:
Title
Determine the optimal dose of VIC-1911 when given in combination with standard immunosuppressive therapy in adult patients undergoing myeloablative stem cell transplantation.
Description
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.
Time Frame
21 days post treatment
Title
Confirm safety and obtain an estimate of long-term efficacy as measured by aGVHD assessed (Phase II)
Description
Assessment for aGVHD
Time Frame
Day 100
Title
Relapsed assessment (Phase II)
Description
Assessment to determine if patient has relapse
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Analyze markers of mTOR and IL-2 activity cells
Description
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
Time Frame
Pre-condition, before Day 1 (Day 0)
Title
Analyze markers of mTOR and IL-2 activity cells
Description
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
Time Frame
Day 21
Title
Analyze markers of mTOR and IL-2 activity cells
Description
Determine the frequency of CD4+, pS6+ [marker of mTOR activity] and CD4+, pSTAT5+ [marker of IL-2 activity] cells
Time Frame
Day 100
Title
To determine the cumulative incidences of acute GVHD
Description
Assessment of aGVHD
Time Frame
Day 100
Title
To determine the cumulative incidences of chronic GVHD
Description
Assessment of cGVHD
Time Frame
12 months
Title
Compare Graft-Versus-Host Disease-Free (GRFS) to the standard PTCY plus tacrolimus/mycophenolate mofetil regimen from MT2015-29
Description
GRFS defined as grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, relapse, or death by 1 year
Time Frame
12 months
Title
Compare duration of initial transplant hospitalization to patients age 18+ who received treatment on MT2015-29
Description
Comparison hospitalization days with another trial's data (MT2015-29)
Time Frame
12 months
Title
To measure Quality of life
Description
Use quality of life questionnaire to measure patients' quality of life.
Time Frame
Through day 100
Title
To analyze the frequency of CMV reactivation and disease
Time Frame
Through day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cancer Center Clinical Trials Office
Phone
612 624 2620
Email
ccinfo@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherman Holtan, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center at University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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