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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02869633
Recruitment Status : Recruiting
First Posted : August 17, 2016
Last Update Posted : October 4, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Madan Jagasia, MD, Vanderbilt-Ingram Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Ibrutinib Other: Laboratory Biomarker Analysis Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Optimizing Post-allogeneic Hematopoietic Cell Transplant Outcomes for Lymphoma Using Ibrutinib
Study Start Date : September 2016
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : October 2020

Arm Intervention/treatment
Experimental: Treatment (ibrutinib)
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
Given by mouth

Other: Laboratory Biomarker Analysis
Correlative studies

Primary Outcome Measures :
  1. Progression free survival [ Time Frame: Time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, assessed at 12 months post HCT ]

Secondary Outcome Measures :
  1. Minimal Residual Disease assessed by sequencing [ Time Frame: Up to 12 months ]
  2. T cell repertoire assessed by IMMUNOSEQ [ Time Frame: Up to 12 months ]
  3. B cell subsets and signaling assessed by mass cytometry [ Time Frame: Up to 12 months ]
  4. T cell subsets and signaling assessed by mass cytometry [ Time Frame: Up to 12 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients undergoing their first T-cell replete allogenic (allo)-hematopoietic cell transplant for chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma (FL), Hodgkin disease (HD)
  • Meeting institutional criteria for allo-hematopoietic cell transplant; ejection fraction by echocardiogram or multi-gated acquisition scan (MUGA) > 40%, pulmonary function test with adjusted diffusion capacity of the lung for carbon monoxide (DLCO) >= 60%
  • Matched (8/8) or mismatched (7/8) related, unrelated hematopoietic cell transplant
  • 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
        • 17 p deletion (detected by any assay) (>= 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 >= 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
        • Relapsed/refractory mantle cell lymphoma >= 1 line of therapy; prior ibrutinib therapy is permitted; prior autologous hematopoietic cell transplant is permitted
        • 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
    • Cohort B

      • Follicular lymphoma

        • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND
        • Relapsed/refractory follicular lymphoma >= 2 lines of therapy; prior ibrutinib therapy is permitted
      • Hodgkin disease

        • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND
        • Relapsed/refractory Hodgkin disease >= 2 lines of therapy
  • Preparative regimen: both reduced intensity and ablative regimens are permitted; each center will pre-specify the regimen they intend to use during the conduct of the study
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for females, these restrictions apply for 1 month after the last dose of study drug; for males, these restrictions apply for 3 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • Prior to Administration of Ibrutinib (Day 60 to Day 90 post hematopoietic cell transplant)
  • Karnofsky performance status (KPS) >= 60%
  • Engraftment of neutrophils (absolute neutrophil count [ANC] >= 1.0 X 10^9/L) for 3 days without granulocyte colony-stimulating factor (g-csf) support
  • Platelets >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement independent of transfusion support in either situation
  • Glomerular filtration rate (GFR) >= 30 ml/min
  • Liver function tests (LFTs) (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) =< 3 X upper limit of normal (ULN)
  • Total bilirubin =< 1.5 mg/dL X ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
  • Predominant donor chimerisms as measured by CD3 and CD33 (or other myeloid marker)
  • DONOR: Human leukocyte antigen (HLA) >= 7/8 related or unrelated donors

Exclusion Criteria:

  • 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 (CNS) 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 human immunodeficiency syndrome (HIV)
  • Active hepatitis B or C virus
  • In the critical care unit, or use of mechanical ventilation or use of renal replacement therapy at any time post hematopoietic cell transplant and prior to administration of ibrutinib
  • Active uncontrolled stage 3-4 acute gastrointestinal (GI) graft versus host disease prior to administration of ibrutinib
  • Active uncontrolled stage 4 acute liver graft versus host disease prior to administration of ibrutinib
  • Evidence of progressive disease as compared to pre-hematopoietic cell transplant (persistence of disease is permitted)
  • Prednisone equivalent of > 2m/kg for treatment of graft versus host disease prior to administration of ibrutinib
  • Use of second line systemic therapy for treatment of acute graft versus host disease prior to administration of ibrutinib
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
  • Major surgery or a wound that has not fully healed within 4 weeks of starting ibrutinib
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
  • Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
  • Vaccinated with live, attenuated vaccines within 4 weeks of starting ibrutinib

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02869633

Contact: VICC Clinical Trials Information Program 800-811-8480

United States, Alabama
University of Alabama at Birmingham Cancer Center Recruiting
Birmingham, Alabama, United States, 35233
Contact: Luciano Costa, M.D.   
United States, California
Stanford Cancer Institute Recruiting
Palo Alto, California, United States, 94304
Contact: David Miklos, M.D.   
United States, Kansas
University of Kansas Cancer Center Not yet recruiting
Kansas City, Kansas, United States, 66160
Contact: Joseph McGuirk, M.D.   
United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Edwin Alyea, M.D.   
United States, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: VICC Clinical Trials Information Program         
Contact    800-811-8480      
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sairah Ahmed, M.D.   
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Madan Jagasia, M.D. Vanderbilt-Ingram Cancer Center

Responsible Party: Madan Jagasia, MD, Principal Investigator, Vanderbilt-Ingram Cancer Center Identifier: NCT02869633     History of Changes
Other Study ID Numbers: VICC BMT 1651
NCI-2016-01246 ( Registry Identifier: NCI, Clinical Trials Reporting Program )
First Posted: August 17, 2016    Key Record Dates
Last Update Posted: October 4, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Leukemia, B-Cell
Lymphoma, Follicular
Leukemia, Lymphoid
Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin