Clinical Trials /

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

NCT02532257

Description:

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.

Related Conditions:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 2015-0361
  • SECONDARY ID: NCI-2015-01513
  • NCT ID: NCT02532257

Conditions

  • Lymphoma
  • Follicular Lymphoma (FL)

Interventions

DrugSynonymsArms
LenalidomideCC-5013, RevlimidLenalidomide + Rituximab + Ibrutinib
RituximabRituxanLenalidomide + Rituximab + Ibrutinib
IbrutinibPCI-32765, ImbruvicaLenalidomide + Rituximab + Ibrutinib

Purpose

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.

Detailed Description

Study Drug Administration:

Each study cycle is 28 days.

You will take lenalidomide by mouth on Days 1-21 of Cycle 1. After Cycle 1, your dose of lenalidomide will increase and you will take it by mouth on Days 1-21 of Cycles 2-12. You should return all empty or leftover lenalidomide capsules/bottles to the study staff. Do not share the study drug with anyone.

You will receive rituximab by vein over about 4-6 hours on Days 1, 8, 15, and 22 of Cycle 1 and then on Day 1 of Cycles 2-12.

You will also receive ibrutinib by mouth 1 time every day of Cycles 1-12. You should take your dose ibrutinib with a cup (about 8 ounces) of water.

Study Visits:

On Day 1 of Cycle 1:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- Blood (about 2-3 teaspoons) will be drawn before your dose of rituximab for biomarker testing . Biomarkers are found in the blood/tissue and may be related to your reaction to the study drugs.

On Days 8, 15, and 22 of Cycle 1:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests. If you can become pregnant, this blood draw will also include a pregnancy test.

- Blood (about 2-3 teaspoons) will be drawn for biomarker testing on Day 15 only.

On Day 1 of Cycles 2 and beyond:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests. If you can become pregnant, this blood draw will also include a pregnancy test.

- During Cycles 4 and 7 only, you will have an MRI or PET/CT scan.

- During Cycles 2 and 7 only, blood (about 2-3 teaspoons) will be drawn for biomarker testing.

Women who can become pregnant and have irregular menstrual periods will have the blood pregnancy test (about 1 teaspoon) repeated on Day 15 of every cycle.

Length of Treatment:

You may receive the study drugs for up to 12 cycles. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on this study will be over after the follow-up visits.

End-of-Treatment Visits:

About 4 weeks after your last dose of study drugs:

- You will have a physical exam.

- Blood (about 4-6 teaspoons) will be drawn for routine tests and biomarker testing.

- You will have an MRI or PET/CT scan.

You will also be asked about any side effects you may have had and if you have been hospitalized.

If you can become pregnant, you will have a pregnancy test when you are taken off lenalidomide. The test will be repeated either 28 days after your last dose (if you have regular or no menstrual cycles), or 14 and 28 days after your last dose (if you have irregular menstrual cycles).

Follow Up Visits:

After the End-of-Treatment visit, you will have follow-up visits every 12 weeks (± 2 weeks) for the first year and then every 24 weeks (± 4 weeks) after that. Follow-up will stop when 3 years have passed since the last study participant enrolled received their last dose of study drug.

If you completed 12 cycles of study treatment, at each follow-up visit:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- You will have an MRI or PET/CT scan.

If you stopped study treatment early because the disease got worse or came back, you will be called and asked about any new therapies you have started, any symptoms you may be having, and about your overall health. Each call should take about 5-10 minutes.

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.

Trial Arms

NameTypeDescriptionInterventions
Lenalidomide + Rituximab + IbrutinibExperimentalParticipants 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.
  • Lenalidomide
  • Rituximab
  • Ibrutinib

Eligibility 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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description: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

Measure:Complete Response (CR)
Time Frame:120 weeks
Safety Issue:
Description:CR determined by the investigator based on the 2014 Cheson Lugano criteria.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Lymphoma
  • Follicular Lymphoma
  • FL
  • Previously untreated
  • Lenalidomide
  • CC-5013
  • Revlimid
  • Rituximab
  • Rituxan
  • Ibrutinib
  • PCI-32765
  • Imbruvica

Last Updated

February 28, 2017