Obinutuzumab and Lenalidomide in Treating Patients With Previously Untreated Stage II-IV Grade 1-3a Follicular Lymphoma

Brief Title

Obinutuzumab and Lenalidomide in Treating Patients With Previously Untreated Stage II-IV Grade 1-3a Follicular Lymphoma

Official Title

A Phase II Study of Obinutuzumab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma

Brief Summary

      This phase II trial studies how well obinutuzumab and lenalidomide work in treating patients
      with previously untreated stage II-IV grade 1-3a follicular lymphoma. Immunotherapy with
      obinutuzumab, may induce changes in body's immune system and may interfere with the ability
      of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in
      different ways to stop the growth of cancer cells, either by killing the cells, by stopping
      them from dividing, or by stopping them from spreading. Giving obinutuzumab and lenalidomide
      may work better in treating patients with previously untreated follicular lymphoma.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the efficacy of obinutuzumab combined with lenalidomide in patients with
      previously untreated follicular lymphoma (FL) (determined by progression-free survival [PFS]
      at 2 years).

      SECONDARY OBJECTIVES:

      I. To evaluate the safety of obinutuzumab in combination with lenalidomide in patients with
      untreated follicular lymphoma.

      II. To evaluate the efficacy of obinutuzumab in combination with lenalidomide in subjects
      with follicular lymphoma as assessed by complete remission (CR) at 30 months, overall
      response rate (ORR), duration of response (DOR), event free survival (EFS), and overall
      survival (OS).

      EXPLORATORY OBJECTIVES:

      I. To evaluate prognostic and predictive biomarkers relative to treatment outcomes.

      OUTLINE:

      Patients receive obinutuzumab intravenously (IV) over 4-6 hours on days 1, 8, and 15 of
      course 1 and day 1 of courses 2-6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30.
      Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or
      unacceptable toxicity. Patients also receive lenalidomide orally (PO) on days 1-21. Treatment
      repeats every 28 days for up to 6 cycles in the absence of disease progression or
      unacceptable toxicity. Patients with CR or complete remission unconfirmed (CRu) may receive
      up to an additional 12 courses of lenalidomide.

      After completion of study treatment, patients are followed up every 6 months for 18 months
      and then every year for up to 2 years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Progression free survival

Secondary Outcome

 Complete response

Condition

Ann Arbor Stage II Grade 1 Follicular Lymphoma

Intervention

Lenalidomide

Study Arms / Comparison Groups

 Treatment (obinutuzumab, lenalidomide)
Description:  Patients receive obinutuzumab IV over 4-6 hours on days 1, 8, and 15 of course 1 and day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, and 30. Treatment repeats every 28 days for up to 30 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR or CRu may receive up to an additional 12 cycles of lenalidomide.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

90

Start Date

December 6, 2016

Completion Date

July 23, 2024

Primary Completion Date

July 23, 2023

Eligibility Criteria

        Inclusion Criteria:

          -  A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated

          -  Able and willing to provide written informed consent and to comply with the study
             protocol

          -  Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest
             diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or
             magnetic resonance imaging (MRI)

          -  Must be in need of therapy as evidenced by at least one of the following criteria:

               -  Bulky disease defined as:

                    -  A nodal or extranodal (except spleen) mass > 7 cm in its greater diameter
                       or,

                    -  At least 3 nodal or extranodal sites >= 3 cm in diameter

               -  Presence of at least one B symptom:

                    -  Fever (> 38 C) not due to infectious etiology

                    -  Night sweats

                    -  Weight loss > 10% in the past 6 months

               -  Fatigue due to lymphoma

               -  Splenomegaly (> 13 cm)

               -  Compression syndrome (ureteral, orbital, gastrointestinal)

               -  Any of the following cytopenias due to lymphoma:

                    -  Hemoglobin =< 10 g/dL

                    -  Platelets =< 100 x 10^9/L

                    -  Absolute neutrophil count (ANC) < 1.5 x 10^9/L

               -  Pleural or peritoneal effusion

               -  Lactate dehydrogenase (LDH) > upper limit of normal (ULN) or beta-2 microglobulin
                  > ULN

          -  Stage II, III, or IV disease

          -  Eastern cooperative oncology group (ECOG) performance status =< 2

          -  Absolute neutrophil count (ANC) > 1.0 x 10^9/L

          -  Platelet count > 75 x 10^9/L

          -  Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 3 x upper limit of
             normal (ULN)

          -  Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula

          -  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 3 g/dL

          -  Women of childbearing potential and men who are sexually active must practice reliable
             contraceptive measures started at least 4 weeks before study therapy and continued for
             at least 4 weeks following discontinuation therapy; females of childbearing potential
             must either completely abstain from heterosexual sexual contact or must use 2 methods
             of reliable contraception; reliable contraceptive methods include 1 highly effective
             method (intrauterine device, birth control pills, hormonal patches, injections,
             vaginal rings, or implants) and at least 1 additional method (condom, diaphragm, or
             cervical cap) every time they have sex with a male; 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

          -  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; females of reproductive potential must
             adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation
             and Mitigation Strategies (REMS) program

          -  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

          -  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

        Exclusion Criteria:

          -  Known active central nervous system lymphoma or leptomeningeal disease

          -  Follicular lymphoma with evidence of diffuse large B-cell transformation

          -  Grade 3b follicular lymphoma

          -  Any prior history of other malignancy besides follicular 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:

               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                  of disease

               -  Adequately treated cervical carcinoma in situ without evidence of disease

          -  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 lenalidomide capsules, or put the study outcomes at undue
             risk

          -  Known history of human immunodeficiency virus (HIV), active hepatitis C virus, active
             hepatitis B virus infection, or any uncontrolled active systemic infection

               -  Patients with inactive hepatitis B infection must adhere to hepatitis B
                  reactivation prophylaxis unless contraindicated

          -  Prior use of lenalidomide

          -  Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc.,
             or chronic administration glucocorticoid equivalent of > 10 mg/day of prednisone)
             within 28 days of the first dose of study drug

          -  Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any
             component of rituximab

          -  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

          -  Significant screening electrocardiogram (ECG) abnormalities including left bundle
             branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree
             block

          -  Vaccinated with live, attenuated vaccines within 4 weeks of study entry

          -  Lactating or pregnant subjects

          -  Administration of any investigational agent within 28 days of first dose of study drug

          -  Patients who have undergone major surgery within 14 days

          -  Patients with the following:

               -  Bleeding diathesis or patients in whom prophylactic antithrombotic therapy is
                  otherwise contraindicated

               -  Patients with prior deep vein thrombosis (DVT), pulmonary embolism (PE), or
                  arterial thromboembolism

               -  Patients with ischemic stroke or transient ischemic attack (TIA)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Loretta J Nastoupil, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02871219

Organization ID

2015-0464

Secondary IDs

NCI-2016-01506

Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Loretta J Nastoupil, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

December 2019