A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients with Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Phase 2

Not yet recruiting

• Conditions: AML (Acute Myelogenous Leukemia); Acute Lymphoid Leukemia (ALL); Acute Leukemia (Category); MDS (Myelodysplastic Syndrome); CML (Chronic Myelogenous Leukemia); CLL (Chronic Lymphocytic Leukemia); Prolymphocyctic Leukemia; Chronic Myelomonocytic Leukemia (CMML); Myeloproliferative Neoplasm (MPN); Lymphoma
• Interventions: Drug: Conditioning Regimen A; Drug: Conditioning Regimen B; Drug: Conditioning Regimen C; Drug: Conditioning Regimen D; Drug: Conditioning Regimen E; Procedure: Hematopoietic Cell Transplantation; Drug: PTCy (50 mg/kg D3, D4); Drug: PTCy (25 mg/kg D3, D4); Drug: Post-transplant Tacrolimus; Drug: Post-transplant Mycophenolate mofetil; Drug: Post-transplant Abatacept; Drug: Post-transplant Ruxolitinib; Other: Study treatment compliance; Other: Prohibited Concomitant Therapy; Other: Permitted Concomitant Therapy

• Registration Number: NCT06859424
• Lead Sponsor: Center for International Blood and Marrow Transplant Research

Brief Summary

The purpose of this clinical trial is to compare drug combinations to learn which drugs work best to prevent graft-versus-host-disease (GVHD) in people who have received a stem cell transplant. The source of stem cells is from someone who is not related and has a different blood cell type than the study participant. The researchers will compare the new drug combination to a standard drug combination. They will also learn about the safety of each drug combination.

Participants will:

* Receive the standard or new drug combination after transplant

* Visit the doctor's office for check-ups and tests after transplant that are routine for most transplant patients

* Take surveys about physical and emotional well-being

* Give blood and stool samples.

Detailed Description

This platform protocol will evaluate the safety and efficacy of post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prophylaxis after mismatched unrelated donor (MMUD) hematopoietic cell transplant (HCT). Participants with malignant hematologic diseases eligible per inclusion criteria, receiving MMUD peripheral blood stem cells (PBSCs) after myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) will be eligible to be enrolled by participating transplant centers. The platform protocol will estimate endpoints and provide a comparator arm for investigational interventional arms (ISAs).

Two investigational ISAs are part of the platform protocol - ACCEL-001 and ACCEL-002. The ISAs describe the specific features of the intervention being studied and treatment of participants assigned to that intervention, the specific target population, sample size required based on comparison to the control arm, specific study objectives, statistical methods for evaluating the interventions, and other specific intervention-related information and assessments. Additional ISAs may be added or closed throughout the lifetime of the trial.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-02-28
• Study First Posted: 2025-03-05
• Last Update Submitted: 2025-03-10
• Last Update Posted: 2025-03-12
• Study Start: 2025-06
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 358

Inclusion Criteria

Not provided

Exclusion Criteria

1. Suitable HLA-matched related or 8/8 high-resolution matched unrelated donor available
2. Subject unwilling or unable to give informed consent, or unable to comply with the protocol including required follow-up and testing
3. Subjects with a prior allogeneic transplant
4. Subjects with an autologous transplant within the past 3 months
5. Subjects who are breastfeeding or pregnant
6. Uncontrolled bacterial, viral or fungal infection at the time of the transplant preparative regimen
7. Concurrent enrollment on a GVHD prevention clinical trial
8. Subjects who undergo desensitization to reduce anti-donor HLA antibody levels prior to transplant
9. Patients who are HIV-positive with persistently positive viral load. HIV-infected patients on effective anti-retroviral therapy (ART) with undetectable viral load within 6 months are eligible for this trial. Patients with well-controlled HIV are eligible provided resistance panels are negative, the patient is compliant with ART, and their disease remains well controlled.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACCEL-002	Study treatment compliance	Intervention 2
ACCEL-002	Prohibited Concomitant Therapy	Intervention 2
ACCEL-002	Permitted Concomitant Therapy	Intervention 2
Control/SOC	Conditioning Regimen A	Shared comparator control group
Control/SOC	Conditioning Regimen B	Shared comparator control group
Control/SOC	Conditioning Regimen C	Shared comparator control group
Control/SOC	Conditioning Regimen D	Shared comparator control group
Control/SOC	Conditioning Regimen E	Shared comparator control group
Control/SOC	Hematopoietic Cell Transplantation	Shared comparator control group
Control/SOC	PTCy (50 mg/kg D3, D4)	Shared comparator control group
Control/SOC	Post-transplant Tacrolimus	Shared comparator control group
Control/SOC	Post-transplant Mycophenolate mofetil	Shared comparator control group
Control/SOC	Study treatment compliance	Shared comparator control group
Control/SOC	Prohibited Concomitant Therapy	Shared comparator control group
Control/SOC	Permitted Concomitant Therapy	Shared comparator control group
ACCEL-001	Conditioning Regimen A	Intervention 1
ACCEL-001	Conditioning Regimen B	Intervention 1
ACCEL-001	Conditioning Regimen C	Intervention 1
ACCEL-001	Conditioning Regimen D	Intervention 1
ACCEL-001	Conditioning Regimen E	Intervention 1
ACCEL-001	Hematopoietic Cell Transplantation	Intervention 1
ACCEL-001	PTCy (25 mg/kg D3, D4)	Intervention 1
ACCEL-001	Post-transplant Tacrolimus	Intervention 1
ACCEL-001	Post-transplant Abatacept	Intervention 1
ACCEL-001	Study treatment compliance	Intervention 1
ACCEL-001	Prohibited Concomitant Therapy	Intervention 1
ACCEL-001	Permitted Concomitant Therapy	Intervention 1
ACCEL-002	Conditioning Regimen A	Intervention 2
ACCEL-002	Conditioning Regimen B	Intervention 2
ACCEL-002	Conditioning Regimen C	Intervention 2
ACCEL-002	Conditioning Regimen D	Intervention 2
ACCEL-002	Conditioning Regimen E	Intervention 2
ACCEL-002	Hematopoietic Cell Transplantation	Intervention 2
ACCEL-002	PTCy (25 mg/kg D3, D4)	Intervention 2
ACCEL-002	Post-transplant Tacrolimus	Intervention 2
ACCEL-002	Post-transplant Mycophenolate mofetil	Intervention 2
ACCEL-002	Post-transplant Ruxolitinib	Intervention 2

Primary Outcome Measures

Name	Time	Method
Graft-versus-host disease-free, relapse-free survival (GRFS)	1 year post-HCT	To compare GRFS following transplantation of a PBSC product from a MMUD between standard-of-care PTCy-based GVHD prophylaxis (the control arm) and the combination of reduced-dose PTCy, abatacept, and tacrolimus.

Secondary Outcome Measures

Name	Time	Method
Graft-versus-host disease-free survival (GFS)	1 year post-HCT	To assess GFS for each of the treatment arms
Non-relapse mortality (NRM)	1 year post-HCT	To assess NRM for each of the treatment arms
Cumulative incidence of relapse and disease progression	1 year post-HCT	To assess the cumulative incidence of relapse and disease progression for each of the treatment arms
Cumulative incidence of neutrophil engraftment	1 year post-HCT	To assess the cumulative incidence of neutrophil engraftment for each of the treatment arms
Infection-free survival (IFS)	1 year post-HCT	To assess IFS for each of the treatment arms
Overall survival (OS)	1 year post-HCT	To assess OS for each of the treatment arms
Progression-free survival (PFS)	1 year post-HCT	To assess PFS for each of the treatment arms
Cumulative incidence of platelet engraftment	1 year post-HCT	To assess the cumulative incidence of platelet engraftment for each of the treatment arms
Primary graft failure (PGS) and secondary graft failure (SGF)	1 year post-HCT	To assess PGF and SGF for each of the treatment arms
Cumulative incidence of aGVHD	1 year post-HCT	To assess the cumulative incidence of aGVHD for each of the treatment arms
Cumulative incidence of cGVHD	1 year post-HCT	To assess the cumulative incidence of cGVHD for each of the treatment arms
Incidence of ≥ grade 2 infections	1 year post-HCT	To assess the incidence of ≥ grade 2 infections for each of the treatment arms (BMT CTN grades II-III infection; Grades 1 ("mild", generally not reported), 2 ("moderate") and 3 ("severe/life threatening"))
Donor cell engraftment	1 year post-HCT	To assess donor cell engraftment for each of the treatment arms
Incidence of cytokine release syndrome (CRS)	1 year post-HCT	To assess the incidence of CRS for each of the treatment arms