This phase II trial studies how well cyclophosphamide and abatacept work in reducing the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following donor stem cell transplantation in patients with hematologic (blood) cancers. GVHD occurs when the cells from the donor (the graft) see the body's cells (the host) as different and attack them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunosuppressive therapy, such as abatacept, is used to decrease the body’s immune response. The combination of cyclophosphamide and abatacept following donor stem cell transplantation may work better in reducing the incidence of moderate and severe chronic GVHD compared to standard of care.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03680092.
PRIMARY OBJECTIVE:
I. To examine if the novel combination of post transplant high dose cyclophosphamide and abatacept can induce tolerance.
SECONDARY OBJECTIVES:
I. To estimate the rate of other important transplant outcomes with the two GVHD prophylaxis strategies:
Ia. Donor engraftment by day 28.
Ib. Grades II-IV and III-IV acute GVHD.
Ic. Chronic GVHD of all grades.
Id. Relapse rate.
Ie. Disease free survival over the course of the study.
If. Overall survival.
Ig. Transplant related mortality by 1 year after transplantation.
II. To estimate the infectious, renal, cognitive and other toxicity caused by the two GVHD prophylaxis strategies.
EXPLORATORY OBJECTIVES:
I. Post-transplantation immune reconstitution studies will include measuring T cell and natural killer (NK) cell phenotype, PD-1 expression, and alloreactivity to recipient and third party at predetermined time points.
II. Compare and contrast the findings between the treatment and control arm and correlate those with disease relapse and presence of acute or chronic GVHD.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I:
CONDITIONING REGIMEN: Patients with matched related or unrelated donor receive fludarabine intravenously (IV) over 60 minutes and busulfan IV over 3 hours on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
Patients with acute lymphoblastic leukemia (ALL) and a matched related or unrelated donor may receive either of the following at the investigator’s discretion: cyclophosphamide IV over 2 hours on days -5 and -4 followed by total body irradiation (TBI) on days -3 to -1; OR TBI on days -7 to -4 followed by etoposide on day -3.
TRANSPLANT: Patients undergo stem cell transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive standard tacrolimus IV starting on day -2 and methotrexate IV on days 1, 3, 6 and 11 in the absence of disease progression or unacceptable toxicity.
ARM II:
CONDITIONING REGIMEN: Patients with matched related or unrelated donor receive fludarabine IV over 60 minutes and busulfan IV over 3 hours on days -6 to -3 in the absence of disease progression or unacceptable toxicity.
Patients with ALL and a matched related or unrelated donor may undergo TBI on days -3 to -1 at the investigator’s discretion.
TRANSPLANT: Patients undergo stem cell transplantation on day 0.
GVHD PROPHYLAXIS: Patients receive abatacept IV on days 5, 14 , 28, 56, 84, 112, 140, and 168, as well as cyclophosphamide IV on days 3 and 4 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year after transplant.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationUC San Diego Medical Center - Hillcrest
Principal InvestigatorDimitrios Tzachanis
