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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

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

NCT ID

NCT05120570

First Posted

November 3, 2021

Last Updated

April 14, 2023

Sponsor

Masonic Cancer Center, University of Minnesota

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

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

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

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

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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