Nivolumab for High-Risk MDS/AML Patients After Allogeneic Stem Cell Transplant With Post-Transplant Cyclophosphamide

Part of paid clinical trials in Denver, Colorado.

Sponsor
SCRI Development Innovations, LLC
Study ID
NCT04361058
Phase
PHASE1
Status
Withdrawn

Conditions

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndrome Acute Myeloid Leukemia
  • Myelodysplastic Syndromes

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Nivolumab — DRUG
    At Day +50 (±10 days) post-allogeneic SCT, participants will be treated with Nivolumab. Nivolumab will be administered intravenously once every two weeks for a total of 4 treatments. Participants will initially receive nivolumab at a significantly reduced starting dose of 0.25 mg/kg. This dose was determined based on the incidence of increased aGVHD, which was noted after treatment post-SCT in previous studies. Nivolumab IV will be given every 2 weeks for 4 cycles. One dose of nivolumab is equivalent to one cycle. The first administration will be at Day +50 (±10 days), assuming the participant has not had any evidence of Grade II-IV aGVHD after allogeneic SCT and does not have any current evidence of any grade of aGVHD at the day of first application of nivolumab. Depending on emerging safety data, dose escalation cohorts will explore higher dose levels of nivolumab at 0.5 mg/kg and 1 mg/kg.

Study Details

There are no strategies developed post-stem cell transplant (SCT) for patients who receive allogenic SCT with a significant amount of blasts prior SCT. Novel strategies to treat relapsed AML/MDS and to reduce the incidence of relapse after allogeneic SCT are needed. This study is being done in patients with high-risk MDS or AML who undergo an allogeneic SCT. The study will have two arms, participants who receive an HLA-matched unrelated donor SCT (Arm A) or HLA- haploidentical SCT (Arm B). Following myeloablative conditioning (MAC), GVHD prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus and mycophenolate mofetil will be given per standard of care. At 40-60 days post SCT, If the patient has not had any evidence of Grade II-IV acute graft-versus-host-disease (aGVHD), Nivolumab will be given intravenously every 2 weeks for 4 cycles of consolidation or treatment with Nivolumab. Dose-escalation of Nivolumab will follow the standard 3+3 design where a maximum of three dose levels will be evaluated, with a maximum of 18 patients treated with nivolumab per arm. As the maximum tolerated dose (MTD) of Nivolumab may differ between Arm A and Arm B, dose escalation of nivolumab in each arm will be followed separately following allogeneic SCT. Immunosuppression with tacrolimus will be continued during the cycles of PD-1 blockade to provide a moderate level of GVHD prophylaxis during consolidation or treatment with nivolumab.

Key Dates

Start date
Apr 13, 2020
Status verified
Apr 2021
Primary completion
Apr 20, 2021
Completion
Apr 20, 2021

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A - HLA-matched unrelated donor SCT treated with Nivolumab
    AML/MDS participants who have allogeneic stem cell transplants with an HLA-matched unrelated donor will be separated into Arm A and treated with Nivolumab post-SCT
  • Experimental: Arm B - HLA-haploidentical donor SCT treated with Nivolumab
    AML/MDS participants who have allogeneic stem cell transplants with a HLA-haploidentical donor will be separated into Arm B and treated with Nivolumab post-SCT

Primary Outcome Measure

Incidence of dose limiting toxicities as a determinant of the Maximum Tolerated Dose (MTD) [ Time Frame: After the first dose of Nivolumab treatment for up to 28 days. ]

Locations (1)

FacilityCityStateZIPSite coordinators
Colorado Blood Cancer InstituteDenverColorado80218-

Find similar trials in Denver, CO

By research site
Colorado Blood Cancer Institute· Denver, CO

Related Studies