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

NCT02877082 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB00082499NCI-2016-01035Winship3258-16
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Total Number of Serious Adverse Events and Adverse Events Related to This Immunosuppressive Regimen

  An adverse event (AE) is defined as any untoward medical experience or change of an existing condition that occurs during or after treatment. All AEs occurring during this study, whether observed by the physician, nurse, or reported by the patient, will be graded per NCI CTCAE version 4.0 and recorded on protocol-specific case report forms. A serious adverse event (SAE) is defined as any expected or unexpected adverse event (AE, generally equivalent to CTCAE grades 3, 4 or 5) that results in any of the following outcomes: * Death * Life-threatening event * In-patient hospitalization (not required as part of the treatment) or prolongation of existing hospitalization * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Cancer * Overdose

  Up to 6 months post-transplant

• Number of Patients Alive and Free of Severe Acute GVHD Following HLA Matched Related or Unrelated Donor Hematopoietic Peripheral Blood Transplant

  Will use patient counts for the number of patients alive and free of severe acute graft versus host disease (GVHD) following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant.

  At 6 months post-transplant

Secondary Outcomes (3)

• Cumulative Incidence of Grade III-IV aGVHD

  Up to 2 years post-transplant

• Incidence of Chronic GVHD

  Up to 2 years post-transplant

• Overall Survival

  At 1 year post-transplant

Study Arms (1)

Tacrolimus, bortezomib, thymoglobulin

EXPERIMENTAL

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.

Biological: Thymoglobulin; Drug: Bortezomib; Drug: Tacrolimus

Interventions

Thymoglobulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Anti-Thymocyte Globulin

Tacrolimus, bortezomib, thymoglobulin

Bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, PS341, Velcade

Tacrolimus, bortezomib, thymoglobulin

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Tacrolimus, bortezomib, thymoglobulin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Graft vs Host Disease; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders

Interventions

thymoglobulin; Antilymphocyte Serum; Bortezomib; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Bone Marrow Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Macrolides; Lactones

Limitations and Caveats

After monitoring early toxicity and hyperacute severe acute graft versus host disease in 4/5 patients, it was decided to close this protocol.

Results Point of Contact

• Title: Zaid Al-Kadhimi, MD
• Organization: Emory University/Winship Cancer Institute

zalkadh@emory.edu

404-778-1900

Study Officials

• Zaid Al-Kadhimi, MD

  Emory University/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: August 24, 2016
• Study Start: September 1, 2016
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: April 30, 2018
• Results First Posted: April 30, 2018

Record last verified: 2018-03

Locations

US (1)