Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients

NCT ID: NCT02877082

Last Updated: 2018-04-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2017-07-31

Brief Summary

This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients with blood cancer who are undergoing donor stem cell transplant. Tacrolimus and anti-thymocyte globulin may reduce the risk of the recipient's body rejecting the transplant by suppressing the recipient's immune system. Giving bortezomib after the transplant may help prevent GVHD by stopping the donor's cells from attacking the recipient. Giving tacrolimus, bortezomib, and anti-thymocyte globulin may be a better way to prevent low toxicity GVHD in patients with blood cancer undergoing donor stem cell transplant.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine a composite end point of alive and severe acute GVHD free at 6 months following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant in patients with hematologic malignancies who receive the immunosuppressive combination tacrolimus, bortezomib, anti-thymocyte globulin (TBT) as GVHD prophylaxis.

II. To determine the safety of this combination in the first six months post-transplant.

SECONDARY OBJECTIVES:

I. To determine the cumulative incidence of grade III-IV aGVHD.

II. To determine incidence and severity of chronic GVHD.

III. To determine disease relapse or progression overall and disease free survival at one year.

OUTLINE:

Patients receive tacrolimus intravenously (IV) on day -3 through day 180. Patients may receive tacrolimus orally (PO) later at the doctor's discretion. Patients receive anti-thymocyte globulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0.

After completion of study treatment, patients are followed up for 6 months and then periodically for up to 2 years.

Conditions

Acute Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Tacrolimus, bortezomib, thymoglobulin

Patients receive tacrolimus IV on day -3 through day 180. Patients may receive tacrolimus PO later at the doctor's discretion. Patients receive thymoglobulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0.

Group Type: EXPERIMENTAL

Thymoglobulin

Intervention Type: BIOLOGICAL

Given IV

Bortezomib

Intervention Type: DRUG

Given IV

Tacrolimus

Intervention Type: DRUG

Given IV and PO

Interventions

Thymoglobulin

Given IV

Intervention Type: BIOLOGICAL

Bortezomib

Given IV

Intervention Type: DRUG

Tacrolimus

Given IV and PO

Intervention Type: DRUG

Other Intervention Names

Antithymocyte Globulin; Antithymocyte Serum; ATG; ATGAM; ATS; Anti-Thymocyte Globulin; LDP 341; MLN341; PS-341; PS341; Velcade; FK 506; Fujimycin; Hecoria; Prograf; Protopic

Eligibility Criteria

Inclusion Criteria

• Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disorder and myelodysplasia with no circulating blasts and with less than 5% blasts in the bone marrow within 4 weeks of the start of transplant conditioning regimen
• Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma; follicular, marginal zone, diffuse large B-cell or mantle cell lymphoma with chemo-sensitive disease at time of transplant
• Patients must have a related or unrelated peripheral blood stem cell donor; sibling donor must be a 6/6 match for human leukocyte antigen (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation; unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing; unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to National Marrow Donor Program (NMDP) criteria
• Cardiac function: ejection fraction > 40%
• Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
• Pulmonary function: carbon monoxide diffusing capability test (DLCO) ≥ 40% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥ 50%
• Total bilirubin < 1.5 x the upper limit of normal; patients who have been diagnosed with Gilbert's disease are allowed to exceed the defined bilirubin value of 1.5 x the upper limit of normal
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper normal limit
• Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception or agree to completely abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
• Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
• Signed informed consent

Exclusion Criteria

• Prior allogeneic transplant
• Karnofsky performance score < 70%
• Active central nervous system (CNS) involvement by malignant cells
• Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
• Patients with transformed lymphoma (e.g., Richter's transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
• Patients seropositive for the human immunodeficiency virus (HIV)
• Patient with active hepatitis B or C
• Patients with hypersensitivity to bortezomib, boron, or mannitol
• Patients with > grade 2 sensory peripheral neuropathy
• Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant
• Female patients who are lactating or pregnant
• Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously will be allowed; cancer treated with curative intent < 5 years previously will not be allowed unless approved by the protocol officer or one of the protocol chairs

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Zaid Al-Kadhimi

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zaid Al-Kadhimi, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University/Winship Cancer Institute

Locations

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2016-01035

Identifier Type: REGISTRY

Identifier Source: secondary_id

Winship3258-16

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00082499

Identifier Type: -

Identifier Source: org_study_id