Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant

NCT02869633 | Completed Phase 2 Results DMC

• 2 other identifiers: VICC CTT 1651NCI-2016-01246
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 5

Brief Summary

This phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Blastoid Variant Mantle Cell Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival Probability at 12-month Post HCT

  The progression free survival (PFS) is defined as time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, starting from the date of stem cell transplant (SCT). This will be restricted to patients in cohort A which includes the diagnoses of CLL and MCL, only, and patients treated with ibrutinib. Twelve-month PFS probability with 95% confidence interval will be estimated using Kaplan-Meier method. This probability range between 0 and 1, and the higher the better.

  Time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, assessed 12 months post HCT.

Secondary Outcomes (4)

• Minimal Residual Disease Assessed by Sequencing

  Up to 12 months

• T Cell Repertoire Assessed by IMMUNOSEQ

  Up to 12 months

• B Cell Subsets and Signaling Assessed by Mass Cytometry

  Up to 12 months

• T Cell Subsets and Signaling Assessed by Mass Cytometry

  Up to 12 months

Study Arms (1)

Treatment (ibrutinib)

EXPERIMENTAL

Beginning between 60-90 days post donor stem cell transplant, patients receive ibrutinib PO QD until 1 year post donor stem cell transplant in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis

Interventions

Ibrutinib DRUG

Given by mouth

Treatment (ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib)

Eligibility Criteria

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

You may qualify if:

• PRE-STEM CELL TRANSPLANT (SCT)
• Patients undergoing their first T cell replete allo-HCT for chronic lymphocytic leukemia (CLL), Hodgkin Lymphoma (HL), or the following subtypes of Non-Hodgkin lymphoma: Mantle cell lymphoma (MCL) and follicular center cell lymphoma (FL)
• Meeting institutional criteria for allo-HCT. Ejection fraction by echocardiogram or MUGA \>40%, pulmonary function test with adjusted DLCO ≥ 60%
• Matched (8/8) or mismatched (7/8) related, unrelated HCT
• Stem cell source: bone marrow, peripheral blood stem cell
• Disease criteria:
• Cohort A
• Chronic lymphocytic leukemia
• Disease burden: lymph node size \< 5 cm and/or extra-nodal involvement \< 5 cm AND
• p deletion (detected by any assay) (\> or equal to 20% of cells involved if assay is conventional cytogenetics or fluorescence in situ hybridization \[FISH\]) or NOTCH mutation at any time point during disease course; patient should have received at least 1 line of therapy; prior ibrutinib therapy is permitted OR
• Relapsed/refractory chronic lymphocytic leukemia \> or equal to 2 lines of therapy; prior ibrutinib therapy is permitted
• Mantle cell lymphoma
• Disease burden: lymph node size \< 5 cm and/or extra-nodal involvement \< 5 cm AND
• Relapsed/refractory mantle cell lymphoma \> or equal to 1 line of therapy. Prior ibrutinib therapy is permitted. Prior autologous hematopoietic cell transplant is permitted. OR
• Mantle cell lymphoma blastoid variant in first complete response (CR1) or high risk mantle cell lymphoma being considered for allo hematopoietic cell transplant in CR1

You may not qualify if:

• PRE-SCT
• Progression of chronic lymphocytic leukemia or mantle cell lymphoma or follicular lymphoma or HD at time of transplant
• Use of Coumadin (warfarin) or other vitamin-K antagonists for anticoagulation; non-Coumadin anticoagulation is permitted
• Known central nervous system involvement
• Active uncontrolled bacterial or invasive fungal infections
• History of malignancy other than the underlying disease unless treated with a curative intent and/or no evidence of disease for at least 3 years (y) OR expected to be cured with SCT
• Planned use of post-hematopoietic cell transplant cyclophosphamide for graft versus host disease prophylaxis
• Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT
• T deplete hematopoietic cell transplant
• Umbilical cord hematopoietic cell transplant
• History of stroke or intracranial hemorrhage within 6 months of enrollment
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known HIV
• Active Hepatitis B or C virus
• Child-Pugh Class C

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Hodgkin Disease; Lymphoma, Mantle-Cell

Interventions

ibrutinib

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; Lymphoma, Non-Hodgkin; Lymphoma

Results Point of Contact

• Title: Teresa Melton
• Organization: Vanderbilt-Ingram Cancer Center

teresa.melton@vumc.org

615-936-7423

Study Officials

• Bhagirathbhai Dholaria, M.D.

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 10, 2016
• First Posted: August 17, 2016
• Study Start: November 1, 2016
• Primary Completion: November 18, 2021
• Study Completion: October 1, 2023
• Last Updated: October 23, 2023
• Results First Posted: January 20, 2023

Record last verified: 2023-10

Locations

US (5)