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Obinutuzumab and Lenalidomide in Treating Patients With Previously Untreated Stage II-IV Grade 1-3a Follicular 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: NCT02871219
Recruitment Status : Active, not recruiting
First Posted : August 18, 2016
Last Update Posted : December 9, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Lenalidomide Biological: Obinutuzumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Obinutuzumab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma
Actual Study Start Date : December 6, 2016
Estimated Primary Completion Date : July 23, 2023
Estimated Study Completion Date : July 23, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Treatment (obinutuzumab, lenalidomide)
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.
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Biological: Obinutuzumab
Given IV
Other Names:
  • Anti-CD20 Monoclonal Antibody R7159
  • GA-101
  • GA101
  • Gazyva
  • huMAB(CD20)
  • R7159
  • RO 5072759




Primary Outcome Measures :
  1. Progression free survival [ 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 ]
    Will be calculated and corresponding 95% confidence interval (CI) will be derived.


Secondary Outcome Measures :
  1. Complete response [ Time Frame: At 120 weeks ]
    The number and percentage of subjects will be tabulated.

  2. Overall response rate (CR + partial response [PR]) [ Time Frame: Up to 3 years ]
    The number and percentage of subjects will be tabulated.

  3. Duration of response [ 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 ]
    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

  4. Event free survival [ 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 ]
    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

  5. Overall survival [ Time Frame: From the date of course 1, day 1 to the date of death regardless of cause, assessed up to 3 years ]
    Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.



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.


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

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): NCT02871219


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Loretta J Nastoupil M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02871219    
Other Study ID Numbers: 2015-0464
NCI-2016-01506 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0464 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 18, 2016    Key Record Dates
Last Update Posted: December 9, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Weight Loss
Fatigue
Splenomegaly
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Body Weight Changes
Body Weight
Signs and Symptoms
Hypertrophy
Pathological Conditions, Anatomical
Lenalidomide
Obinutuzumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Immunological