Obinutuzumab in cGVHD After Allogeneic Peripheral Blood Stem Cell Transplantation

Therapuetic Areas:Hematology
Age Range:18 - Any
Start Date:November 29, 2016
End Date:February 2024
Contact:Corey Cutler, MD MPH

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A Randomized Phase 2 Study of Obinutuzumab for Prevention of Chronic Graft-vs.-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation

This research study is studying a drug called obinutuzumab as a means of preventing chronic
Graft vs. Host Disease (cGVHD).

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease.

The FDA (the U.S. Food and Drug Administration) has not approved Obinutuzumab for prevention
of chronic Graft-vs.-Host Disease (cGVHD), but it has been approved for other uses.

In this research study, the investigators are aiming to determine the effect of Obinutuzumab
on the incidence of corticosteroid-requiring cGVHD after allogeneic Hematopoetic Cell
Transplant (aHCT).

Chronic GVHD is a medical condition that can occur after bone marrow or stem cells are
transplanted from one individual to another. After the transplant, the donor immune system
may recognize the recipient body as foreign and may attempt to 'reject' the body. This
process is referred to as Graft-vs. -Host Disease and may occur at any time, although
generally not earlier than one hundred days after transplantation.

The immune system produces two types of lymphocytes (white blood cells), B cells and T cells.
B cells are part of the 'memory' for the immune system, and they make antibodies (proteins)
when bacteria, viruses or other potentially harmful materials enter the body. Obinutuzumab is
an antibody, a molecule that targets certain cells by binding to specific parts of the target
cell. In this case, Obinutuzumab will bind to a component of B cells called CD20, resulting
in the B cell getting killed. It is thought that reducing the number of B cells will reduce
the chances of developing cGVHD after transplant. Previous studies with another antibody
targeting CD20 on B cells suggests that there may be a reduced chance of developing cGVHD and
the need to prescribe Corticosteroids to treat cGVHD when B cells are killed.

This is a randomized, placebo controlled trial. This means that approximately half of the
study participants will receive Obinutuzumab, and the other half will receive a placebo
(saline solution). A computer will decide which participants will receive Obinutuzumab or
placebo, and neither the participant or the study doctor will know which the participant has
received until the study is completed. It is important to note that the current standard is
to receive no therapy specifically to prevent cGVHD.

Inclusion Criteria:

- 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 DR1), 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 PCR-SSP techniques and CDC techniques. Class II
typing is performed by PCR-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 PET-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 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).

- Age ≥ 18.0

- ECOG performance status ≤2 (Karnofsky ≥60%) (See Appendix A)

- Participants must have normal marrow function as defined by:

- WBC ≥ 2,500/μL

- Absolute Neutrophil Count ≥ 1,000/μL

- Platelets ≥ 50,000/μL

- 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

Exclusion Criteria:

- 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
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.

- 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 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

- Pregnancy or lactation. Negative pregnancy test is required within the screening

- Active use of any other investigational agents.
We found this trial at
185 Cambridge Street
Boston, Massachusetts 02114
Principal Investigator: Yi-Bin Chen, MD
Phone: 617-726-5765
Boston, MA
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450 Brookline Ave
Boston, Massachusetts 2215
Principal Investigator: Correy Cutler, MD MPH
Phone: 617-632-3470
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
Boston, MA
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Palo Alto, California 94304
Palo Alto, CA
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