Clinical trial NCT03680092: Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation
Official title: A Randomized Phase II Trial Comparing a Calcineurin Inhibitor-free Graft-versus-host Disease Prophylaxis Regimen With Post-transplantation Cyclophosphamide and Abatacept to Standard of Care
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: GVHD
Hematologic Neoplasms
Keywords: cancer
Graft-Versus-Host Disease
Hematologic Neoplasms
Abatacept
Cyclophosphamide
GVHD prophylaxis
stem cell transplantation
High risk hematologic malignancy
hematologic malignancy
Allogeneic Hematopoetic Stem Cell Transplantation
GVHD
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2018-09-21
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: GVHD- and Relapse- Free Survival by One Year Post Transplant
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Dimitrios Tzachanis, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Divya Koura, MD
role: PRINCIPAL_INVESTIGATOR
References: