Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation

Phase 2

Active, not recruiting

• Conditions: GVHD; Hematologic Neoplasms
• Interventions: Drug: Cyclophosphamide; Drug: Methotrexate; Drug: abatacept; Drug: Tacrolimus

• Registration Number: NCT03680092
• Lead Sponsor: Dimitrios Tzachanis, MD PhD

Brief Summary

The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.

Detailed Description

The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.

Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.

In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.

The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.

The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)

The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.

The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.

Study Timeline

• Study First Submitted: 2018-09-19
• Study First Submitted QC: 2018-09-20
• Study First Posted: 2018-09-21
• Study Start: 2019-11-26
• Primary Completion: 2023-06-08
• Results First Submitted: 2024-09-04
• Results First Submitted QC: 2024-09-04
• Results First Posted: 2024-10-02
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-27
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma
• Creatinine clearance > 40
• Adequate hepatic function
• Normal cardiac function (EF > 50%)

Exclusion Criteria

• Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
• Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
• Active malignant disease relapse
• Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
• Life expectancy <3 months
• Pregnancy or lactation
• Patients may not be receiving any other investigational agents in the last 28 days
• Patients with chronic myeloid leukemia in first chronic phase

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide and abatacept	abatacept	The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
Cyclophosphamide and abatacept	Cyclophosphamide	The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168
methotrexate and tacrolimus	Tacrolimus	The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus
methotrexate and tacrolimus	Methotrexate	The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus

Primary Outcome Measures

Name	Time	Method
Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant	through study completion, an average of 1 year	The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria

Secondary Outcome Measures

Name	Time	Method
GVHD- and Relapse- Free Survival by One Year Post Transplant	through study completion, an average of 1 year	GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria

Trial Locations

Locations (1)

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States