Obinutuzumab in Preventing Chronic Graft Versus Host Disease in Patients Undergoing Donor Stem Cell Transplant
- Subjects deemed potentially eligible by their treating physicians will be screened for enrollment after d+60 from transplantation
- Patients who have undergone either ablative or non-myeloablative allogeneic stem cell transplantation are eligible
- Peripheral blood stem cells must have been used as the stem cell source
- Patients must have received transplantation from donors (both related and unrelated) who are identical at 8 HLA loci (A, B, C and DRbeta1), or mismatched at no more than 1 locus (7/8); among related donors, HLA C typing is not required (6/6 HLA matches); class I typing is to be performed by polymerase chain reaction (PCR)-sequence specific primers (SSP) techniques and complement-dependent cytotoxicity (CDC) techniques; class II typing is performed by PCR-restriction fragment length polymorphism (RFLP) +/- PCR-SSP techniques
- No evidence of relapsed or residual malignancy within 30 days of trial entry; all patients must undergo appropriate staging for their malignancy (i.e. bone marrow aspiration for the leukemias and positron emission tomography [PET]-computed tomography [CT] scanning for the lymphomas); evidence of a persistent cytogenetic abnormality will constitute evidence of residual or relapsed disease in the leukemias, where present; individuals with chronic lymphocytic leukemia (CLL) are eligible if there is no more than 20% residual leukemia in the bone marrow at the time of study entry
- Patients who have undergone a non-myeloablative stem cell transplant must have > 80% donor hematopoiesis within 30 days of study enrollment; chimerism within 30 days of study entry must be greater than, equal to, or no more than 5% less than the chimerism measured at approximately day +30 (if performed)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- White blood cell (WBC) >= 2,500/uL
- Absolute neutrophil count >= 1,000/uL
- Platelets >= 50,000/uL
- Ability to understand and the willingness to sign a written informed consent document
- The effects of obinutuzumab on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of obinutuzumab administration
- Allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow
- Allogeneic stem cell transplantation using in vivo or ex vivo T cell depletion, either by cell manipulation or with T cell depleting antibodies (any anti-thymocyte globulin preparation or alemtuzumab given within 30 days of transplantation)
- Participation in a clinical trial evaluating another preventative strategy for chronic graft-versus-host disease (GVHD), or ongoing participation in a clinical trial for therapy of acute GVHD; prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 30 days prior to enrollment
- Any evidence of ongoing gastrointestinal or hepatic acute GVHD, or evidence of greater than ongoing stage I cutaneous acute GVHD; ongoing, tapering therapy for resolved acute GVHD is permissible
- Any evidence of prior active or resolved chronic GVHD
- Any evidence of cGVHD or late acute graft versus host disease (aGVHD) between enrollment and first dose of obinutuzumab
- History of severe allergic reaction to obinutuzumab
- No donor lymphocyte infusion (DLI) prior to day 100, and no plans for a DLI in the upcoming 30 days
- Evidence of any active uncontrolled infection (bacterial, viral or fungal) or evidence of natural exposure to hepatitis B, hepatitis C or human immunodeficiency virus (HIV); evidence of hepatitis B exposure includes the presence of hepatitis B surface antigenemia, a positive serological test for hepatitis B core antibody or nucleic acid testing (NAT testing) that is positive for hepatitis B; vaccination to hepatitis B is not an exclusion criteria; testing done in the pre-transplant setting is sufficient to rule out infection
- Pregnancy or lactation; negative pregnancy test is required within the screening window for women of child bearing potential
- Active use of any other investigational agents
Salt Lake City
I. To determine the effect of obinutuzumab prophylaxis on the incidence of corticosteroid-requiring cGVHD after allogeneic hematopoietic cell transplantation (HCT).
I. To determine the overall rate of cGVHD after HCT, the rate of National Institutes of Health (NIH) moderate-severe cGVHD after HCT, the cumulative incidence of non-relapse mortality and relapse, adverse hematologic events and infections, immunosuppression-free survival (IFS) at 1 and 2 years from transplantation, progression-free and overall survival at 1 and 2 years from transplantation, and immunologic correlates of B cell depletion.
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM I: Patients receive obinutuzumab intravenously (IV) over 4.25 hours at 90 days, and over 3.25 hours at 180, 270, and 365 days after HCT.
ARM II: Patients receive placebo IV over 4.25 hours at 90 days, and over 3.25 hours at 180, 270, and 365 days after HCT.
After completion of study treatment, patients are followed up for 2 years.
Trial Phase Phase II
Trial Type Prevention
Dana-Farber Harvard Cancer Center
Corey S. Cutler
- Primary ID 16-256
- Secondary IDs NCI-2016-01860
- Clinicaltrials.gov ID NCT02867384