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

Primary Purpose

Ann Arbor Stage II Grade 1 Follicular Lymphoma, Ann Arbor Stage II Grade 2 Follicular Lymphoma, Ann Arbor Stage III Grade 1 Follicular Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Lenalidomide
Obinutuzumab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ann Arbor Stage II Grade 1 Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (obinutuzumab, lenalidomide)

Arm 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.

Outcomes

Primary Outcome Measures

Progression free survival
Will be calculated and corresponding 95% confidence interval (CI) will be derived.

Secondary Outcome Measures

Complete response
The number and percentage of subjects will be tabulated.
Overall response rate (CR + partial response [PR])
The number and percentage of subjects will be tabulated.
Duration of response
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Event free survival
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Overall survival
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Full Information

First Posted
August 15, 2016
Last Updated
August 29, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02871219
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 6, 2016 (Actual)
Primary Completion Date
July 23, 2024 (Anticipated)
Study Completion Date
July 23, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ann Arbor Stage II Grade 1 Follicular Lymphoma, Ann Arbor Stage II Grade 2 Follicular Lymphoma, Ann Arbor Stage III Grade 1 Follicular Lymphoma, Ann Arbor Stage III Grade 2 Follicular Lymphoma, Ann Arbor Stage IV Grade 1 Follicular Lymphoma, Ann Arbor Stage IV Grade 2 Follicular Lymphoma, Bulky Disease, Fatigue, Fever, Grade 3a Follicular Lymphoma, Night Sweats, Splenomegaly, Weight Loss

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (obinutuzumab, lenalidomide)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
CC-5013, CC5013, CDC 501, Revlimid
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
Obinutuzumab
Other Intervention Name(s)
Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Progression free survival
Description
Will be calculated and corresponding 95% confidence interval (CI) will be derived.
Time Frame
From the treatment start date (course 1, day 1) until the first date of objectively documented progressive disease or date of death from any cause, assessed at 2 years
Secondary Outcome Measure Information:
Title
Complete response
Description
The number and percentage of subjects will be tabulated.
Time Frame
At 120 weeks
Title
Overall response rate (CR + partial response [PR])
Description
The number and percentage of subjects will be tabulated.
Time Frame
Up to 3 years
Title
Duration of response
Description
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time Frame
From the time by which measurement criteria for CR or PR, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 3 years
Title
Event free survival
Description
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time Frame
From the date of course 1, day 1 to the date of first documented progression, transformation to diffuse large B-cell lymphoma, initiation of new anti-lymphoma treatment, or death, assessed up to 3 years
Title
Overall survival
Description
Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.
Time Frame
From the date of course 1, day 1 to the date of death regardless of cause, assessed up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loretta J Nastoupil
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

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

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