Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02532257
Recruitment Status : Active, not recruiting
First Posted : August 25, 2015
Last Update Posted : June 19, 2019
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if adding Imbruvica (ibrutinib) to Rituxan (rituximab) and Revlimid (lenalidomide) can help to control previously untreated follicular lymphoma (FL) and marginal zone lymphoma.

This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenstrom's macroglobulinemia. Lenalidomide is FDA approved and commercially available for the treatment of multiple myeloma (MM), mantle cell lymphoma, and myelodysplastic syndrome (MDS). Rituximab is FDA approved and commercially available for the treatment of non-Hodgkin lymphoma (NHL).

It is considered investigational to use ibrutinib, lenalidomide, and rituximab to treat FL and marginal zone lymphoma.

Up to 60 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Lymphoma Follicular Lymphoma (FL) Drug: Lenalidomide Drug: Rituximab Drug: Ibrutinib Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma
Actual Study Start Date : April 11, 2016
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : April 2021


Arm Intervention/treatment
Experimental: Lenalidomide + Rituximab + Ibrutinib
Participants receive 12 cycles of Lenalidomide, 15 mg daily on Days 1 - 21 of Cycle 1, and 20 mg daily on Days 1 - 21 of Cycles 2 through 12. Cycles are 28 days in length. Participants receive Rituximab, 375 mg/m2 on Days 1, 8, 15, and 22 of Cycle 1, and Day 1 of Cycles 2 through 12. Participants receive Ibrutinib 560 mg daily, starting on Day 1 of Cycle 1 and continued through 12 cycles.
Drug: Lenalidomide
15 mg by mouth on Days 1-21 of Cycle, and 20 mg on Days 1 - 21 of Cycles 2 - 12.
Other Names:
  • CC-5013
  • Revlimid

Drug: Rituximab
375 mg/m2 by vein on Days 1, 8, 15, and 22 of Cycle 1, and Day 1 of Cycles 2 through 12.
Other Name: Rituxan

Drug: Ibrutinib
560 mg by mouth daily, starting on Day 1 of Cycle 1 and continued through 12 cycles.
Other Names:
  • PCI-32765
  • Imbruvica




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    PFS defined as the time from the treatment start date (Cycle 1, Day 1) until the first date of objectively documented progressive disease or date of death from any cause. Response assessed by the investigator based on the 2014 Cheson Lugano criteria.


Secondary Outcome Measures :
  1. Complete Response (CR) [ Time Frame: 120 weeks ]
    CR determined by the investigator based on the 2014 Cheson Lugano criteria.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Histologically confirmed CD20+ follicular lymphoma, grade 1, 2, or 3a or marginal zone lymphoma.
  2. Have had no prior systemic treatment for lymphoma
  3. Bi-dimensionally measurable disease, with at least one mass lesion >/=2 cm in longest diameter by CT, PET/CT, and/or MRI.
  4. In the opinion of the investigator would benefit from systemic therapy
  5. Stage II, III, or IV disease
  6. Must be >/=18 years of age
  7. Eastern Cooperative Oncology Group (ECOG) performance status </=2
  8. Adequate hematologic function within 28 days prior to signing informed consent, including: a. Absolute neutrophil count (ANC) >/=1,000/mm^3, independent of growth factor support b. Platelet counts >/=100,000/mm^3 or >/=50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation
  9. Adequate organ function, including: a. Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper limit of normal (ULN) b. Creatinine clearance >30 ml/min calculated by modified Cockcroft-Gault formula. c. Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3g/dL. d Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
  10. Must be able to adhere to the study visit schedule and other protocol requirements
  11. 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 (females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective [intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants] and at least 1 additional method [condom, diaphragm, cervical cap] of birth control. Reliable contraceptive methods must be started at least 4 weeks before lenalidomide.
  12. 11. continued : Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during and after the study. For females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 1 month after the last dose of study drug. For males, these restrictions apply during the period of therapy and for 3 months after the last dose of study drug.
  13. 12). Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [Beta-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study. a) Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
  14. 13). 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.
  15. 14). All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.

Exclusion Criteria:

  1. Known active central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission > 6 months.
  2. Evidence of diffuse large B-cell transformation
  3. Grade 3b FL
  4. Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for >/= 5 years and felt to be at low risk for recurrence by the treating physician, except: a. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; b. Adequately treated cervical carcinoma in situ without evidence of disease.
  5. 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 or lenalidomide capsules, or put the study outcomes at undue risk, including but not limited to: a. Moderate to severe hepatic impairment (Child-Pugh classes B and C)
  6. Known history of human immunodeficiency virus (HIV), or active Hepatitis C Virus, or active Hepatitis B Virus infection, or any uncontrolled active systemic infection a. Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated.
  7. Prior use of ibrutinib or other BTK inhibitors, rituximab or lenalidomide
  8. Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of >10mg/day of prednisone) within 28 days of the first dose of study drug.
  9. Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab
  10. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon). If patients have been on warfarin or equivalent vitamin K antagonists in the past, they will not be eligible if administered within 30 days of the first dose of study drug.
  11. Requires chronic treatment with strong CYP3A inhibitors, for a list of strong CYP3A inhibitors, see the protocol. If patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug.
  12. Requires chronic treatment with strong CYP3A inducers, for a list of strong CYP3A inducers, see the protocol. If patients have been on a strong CYP3A inducer in the past, they will not be eligible if the CYP3A inducer was administered within 7 days of the first dose of study drug.
  13. 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.
  14. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block.
  15. Known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
  16. History of stroke or intracranial hemorrhage within 6 months prior to study entry.
  17. Vaccinated with live, attenuated vaccines within 4 weeks of study entry
  18. Lactating or pregnant subjects
  19. Administration of any investigational agent within 28 days of first dose of study drug.
  20. Patients who have undergone major surgery within 7 days or minor surgery within 3 days of first dose of study drug.

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 ClinicalTrials.gov identifier (NCT number): NCT02532257


Locations
Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Janssen, LP
Investigators
Layout table for investigator information
Principal Investigator: Loretta Nastoupil, MD M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02532257     History of Changes
Other Study ID Numbers: 2015-0361
NCI-2015-01513 ( Registry Identifier: NCI CTRP )
First Posted: August 25, 2015    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
Follicular Lymphoma
FL
Previously untreated
Lenalidomide
CC-5013
Revlimid
Rituximab
Rituxan
Ibrutinib
PCI-32765
Imbruvica

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Rituximab
Lenalidomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors