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
|Condition or disease||Intervention/treatment||Phase|
|Acute Leukemia Myelodysplastic Syndromes Myeloproliferative Neoplasm Lymphoma||Drug: VIC- 1911||Phase 1 Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|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|
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.
- 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.
- Confirm safety and obtain an estimate of long-term efficacy as measured by aGVHD assessed (Phase II) [ Time Frame: Day 100 ]Assessment for aGVHD
- Relapsed assessment (Phase II) [ Time Frame: 12 months ]Assessment to determine if patient has relapse
- 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
- 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
- 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
- To determine the cumulative incidences of acute GVHD [ Time Frame: Day 100 ]Assessment of aGVHD
- To determine the cumulative incidences of chronic GVHD [ Time Frame: 12 months ]Assessment of cGVHD
- 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
- 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)
- To measure Quality of life [ Time Frame: Through day 100 ]Use quality of life questionnaire to measure patients' quality of life.
- To analyze the frequency of CMV reactivation and disease [ Time Frame: Through day 180 ]
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
|Contact: Cancer Center Clinical Trials Office||612 624 email@example.com|
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Sherman Holtan, MD||Masonic Cancer Center, University of Minnesota|