Belimumab in Preventing Chronic Graft Versus Host Disease after Donor Stem Cell Transplant in Patients with Hematologic Malignancies

Status: Active

Description

This pilot phase I trial studies the side effects of belimumab in preventing chronic graft versus host disease after a donor stem cell transplant in patients with hematologic malignancies. Sometimes the transplanted cells from a donor can attack the body's normal cells, called graft versus host disease. Giving belimumab after the transplant may stop this from happening.

Eligibility Criteria

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Diagnosis of hematologic malignancy (i.e. acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, myelodysplastic syndrome, chronic myelomonocytic leukemia) in complete remission at the time of transplant
  • Use of myeloablative conditioning regimen or non-myeloablative conditioning regimen
  • Use of mobilized peripheral blood stem cells from fully human leukocyte antigen (HLA)-matched related or unrelated donor as a graft source
  • Acute GvHD prophylaxis with methotrexate and tacrolimus
  • Documented complete remission with full donor engraftment (by short tandem repeat [STR] identity testing) on day +30 bone marrow biopsy * Complete remission: less than 5% blasts in an aspirate bone marrow sample with a count of at least 200 nucleated cells, no blasts with auer rods or persistence of extramedullary disease PLUS absolute neutrophil count (ANC) > 1,500/uL, platelet count >= 50,000/uL and no leukemic blasts in the peripheral blood * Negative minimal residual disease * Full donor engraftment by STR testing (either by bone marrow or peripheral blood testing)
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
  • Creatinine clearance >= 40 mL/min/1.73 m^2 by the Cockcroft-Gault formula
  • Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 16 weeks after the last dose of study drug; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent

Exclusion Criteria

  • Active grade III-IV classic acute GvHD; subjects with prior resolved acute GvHD on stable doses of immunosuppression at time of enrollment will be permitted
  • Evidence of classic chronic GvHD or overlap chronic GvHD at time of enrollment
  • Subjects who participated in a clinical trial of acute GvHD prophylaxis in which chronic GvHD was a secondary end point
  • Donor lymphocyte infusion administered to treat relapse or loss of donor chimerism
  • Treatment with rituximab or other anti-B cell specific antibodies within previous 3 months
  • History of other malignancy =< 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix
  • Currently receiving any other investigational agents
  • Known allergy or intolerance to any component of belimumab, including human or murine proteins or monoclonal antibodies
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations (including current drug or alcohol abuse or dependence, or history of drug or alcohol abuse or dependence within the last year) that would limit compliance with study requirements
  • Use of parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 14 days prior to planned start of therapy
  • Evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months and/or poses a significant suicide risk in the judgment of the investigator
  • History of pre-existing immunodeficiency disorder, autoimmune condition, or chronic infection
  • Known human immunodeficiency virus (HIV) positivity
  • Serologic evidence of current or past hepatitis B infection based on the results of testing for hepatitis B virus surface antigen (HBsAg) and anti-hepatitis B virus core (HBc) – patients positive for HBsAg or hepatitis B virus core antibody (HBcAb) are excluded
  • Positive test for hepatitis C antibody (patients with documented clearance of hepatitis C by polymerase chain reaction [PCR] following treatment will be permitted)
  • Currently on therapy for active chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); prophylactic therapy is allowed
  • Has any other clinically significant abnormal laboratory value in the opinion of the investigator

Locations & Contacts

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Iskra Pusic
Phone: 314-454-8304
Email: iskrapusic@wustl.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate safety and tolerability of belimumab as prophylaxis of chronic graft-versus-host disease (GvHD) in subjects following allogeneic hematopoietic stem cell transplantation (alloHCT).

SECONDARY OBJECTIVES:

I. To evaluate the impact of prophylactic belimumab on the incidence and severity of chronic GvHD at 6, 12 and 24 months after alloHCT.

II. To evaluate the impact of prophylactic belimumab on the incidence and severity of acute GvHD at 3 and 6 months after alloHCT.

III. To evaluate the impact of prophylactic belimumab on overall survival at 6, 12 and 24 months after alloHCT.

IV. To evaluate the impact of prophylactic belimumab on relapse rate at 6, 12 and 24 months after alloHCT.

V. To evaluate the impact of prophylactic belimumab on overall corticosteroid requirement (dose and duration) for treatment of chronic GvHD at 6, 12 and 24 months after alloHCT.

VI. To evaluate the impact of prophylactic belimumab on the necessity to use alternative treatment modalities for chronic GvHD at 6, 12 and 24 months after alloHCT.

EXPLORATORY OBJECTIVES:

I. To evaluate the effect of prophylactic belimumab on post-transplant immune cell reconstitution.

II. To explore candidate biomarkers (i.e. BAFF level, BAFF:B cell ratio; B cell subpopulation frequency) that could predict subjects who may benefit from prophylactic administration of belimumab to prevent chronic GvHD.

OUTLINE:

Between 30-80 days post-transplant, patients receive belimumab intravenously (IV) over 1 hour every 2 weeks for 3 courses and then every 4 weeks for a total of 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 24 months, and then at 3, 4, and 5 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Iskra Pusic

Trial IDs

Primary ID 201709068
Secondary IDs NCI-2017-01749
Clinicaltrials.gov ID NCT03207958