Ignite Creation Date:
2025-12-25 @ 12:20 AM
Ignite Modification Date:
2025-12-25 @ 10:24 PM
Study NCT ID:
NCT04361058
Status:
WITHDRAWN
Last Update Posted:
2023-12-05
First Post:
2020-04-15
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Nivolumab for High-Risk MDS/AML Patients After Allogeneic Stem Cell Transplant With Post-Transplant Cyclophosphamide
Sponsor:
SCRI Development Innovations, LLC
Organization:
Study Overview
Official Title:
Graft-Versus-Tumor Augmentation With Nivolumab for High-Risk Patients With MDS and AML After Allogeneic Stem Cell Transplantation Using Post-Transplantation Cyclophosphamide
Status:
WITHDRAWN
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The single site that was deemed appropriate for this study was unable to enroll patients. Closed due to slow accrual.
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
Detailed Description:
There are no strategies developed post SCT for patients who receive allogenic SCT with a significant amount of blasts prior SCT. Historically, the risk of relapse for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is estimated to be 60% to 80%. No standard consolidation treatment options for patients with AML/MDS have been established to decrease the risk of relapse. The options are also limited for patients with relapsed disease after allogeneic SCT. Thus, novel strategies to treat relapsed disease and to reduce the incidence of relapse after allogeneic SCT are needed. PD-1 inhibition can induce remission in patients with relapsed hematologic disease after allogeneic SCT, but the major risk of PD-1 blockade after allogeneic SCT remains the promotion of severe GVHD leading to death. Alternative approaches are needed to reduce the incidence of GVHD after PD-1 blockade while maintaining a strong graft-versus-tumor (GVT) effect. Adding post-transplantation cyclophosphamide (PTCy) prior to PD-1 blockade after an allogeneic SCT may potentially reduce the expected incidence of acute GVHD and prevent relapse by enhancing the GVT effect. As the absence of GVHD has been associated with increased incidence of relapse, it is reasonable to investigate high-risk patients in CR without evidence of GVHD after allogeneic SCT. Since early relapse or progression of disease after allogeneic SCT is associated with a very poor outcome and treatment options are limited, it is also reasonable investigate patients with persistent or progressive disease after allogeneic SCT. At present, no prospective studies have been conducted post-allogeneic SCT using PTCy followed by PD-1 inhibition as a consolidation therapy or as a therapy for persistent or progressive disease. PD-1 blockade after PTCy appears to be safe and does not induce GVHD when compared to patients who did not receive PD-1 blockade after PTCy. As a means to reduce the risk of relapse or provide potentially effective treatment for persistent/progressive disease, this strategy may also avoid the harm of inducing GVHD or possibly exacerbating previously existing GVHD.
This is a multi-center, open-label, double-arm Phase I dose-escalation study of patients with high-risk MDS and AML prior to receiving allogeneic SCT. A maximum of 36 patients (maximum 18 patients per arm) are planned to be screened and enrolled prior to allogeneic SCT with the expectation that each patient will be a suitable candidate for study participation at the time of administration of nivolumab.
Following myeloablative conditioning (MAC) and HLA-matched unrelated donor SCT (Arm A) or HLA- haploidentical SCT (Arm B), GVHD prophylaxis with PTCy, tacrolimus and mycophenolate mofetil will be given per standard of care.
At 40-60 days post SCT, patients without evidence of aGVHD will begin 4 cycles of consolidation or treatment with nivolumab. 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.
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. 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. 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 patient 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.
Participants will be followed for up to 1 year post-SCT and have long-term follow-up will be from 1.5 up to 3 years post-SCT for adverse events, progression or relapse, survival, and evidence of GVHD.
Chronic GVHD staging and grading will be assessed for efficacy as per National Institutes of Health Consensus criteria. Safety and tolerability will be assessed as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
This is a multi-center, open-label, double-arm Phase I dose-escalation study of patients with high-risk MDS and AML prior to receiving allogeneic SCT. A maximum of 36 patients (maximum 18 patients per arm) are planned to be screened and enrolled prior to allogeneic SCT with the expectation that each patient will be a suitable candidate for study participation at the time of administration of nivolumab.
Following myeloablative conditioning (MAC) and HLA-matched unrelated donor SCT (Arm A) or HLA- haploidentical SCT (Arm B), GVHD prophylaxis with PTCy, tacrolimus and mycophenolate mofetil will be given per standard of care.
At 40-60 days post SCT, patients without evidence of aGVHD will begin 4 cycles of consolidation or treatment with nivolumab. 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.
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. 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. 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 patient 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.
Participants will be followed for up to 1 year post-SCT and have long-term follow-up will be from 1.5 up to 3 years post-SCT for adverse events, progression or relapse, survival, and evidence of GVHD.
Chronic GVHD staging and grading will be assessed for efficacy as per National Institutes of Health Consensus criteria. Safety and tolerability will be assessed as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| CA209-9WP | OTHER | Bristol-Myers Squibb | View |