WithdrawnPhase 1

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

Stopped: The single site that was deemed appropriate for this study was unable to enroll patients. Closed due to slow accrual.

United States0Started 2020-04-13

Plain-language summary

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.

Who can participate

Age range18 Years – 65 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria for initial enrollment: * Written informed consent form (ICF), according to local guidelines, signed by the patient or by a legal guardian prior to the performance of any study-related screening procedures (i.e., prior to conditioning). * Male and female patients between ≥18 and ˂66 years-of-age * Patients with high-risk AML defined as: AML with ≥5% bone marrow blast burden prior to allogeneic SCT who failed ≥2 lines of cytoreductive anti-leukemic therapy * Patients with high risk MDS defined as: MDS with ≥10% bone marrow blasts prior to allogeneic SCT despite 1 line of prior cytoreductive anti-leukemic treatment with chemotherapy or hypomethylating agent * Patients will receive a MAC MUD or MAC haploidentical SCT followed by PTCy as treatment for AML or MDS. * A 10/10 HLA-match is required for patients that will receive a MUD SCT. * A 5/10 HLA-match or greater is required for patients that will receive a haploidentical SCT. * Patients must be able to swallow and retain oral medication. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or Inclusion Criteria after SCT, prior to start of nivolumab: * Patients who have achieved a CR post-allogeneic SCT * Patients who have persistent disease post-allogeneic SCT * Greater than 50% PB donor T cell chimerism * Adequate renal function defined as serum creatinine ≤2.0 mg/dL or creatinine clearance ≥40 mL/min measured or calculated by Cockcroft-Gault equation. * Females of childbearing …

What they're measuring

Incidence of dose limiting toxicities as a determinant of the Maximum Tolerated Dose (MTD)

Timeframe: After the first dose of Nivolumab treatment for up to 28 days.

Trial details

NCT IDNCT04361058

SponsorSCRI Development Innovations, LLC

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2021-04-20