- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01995669
Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma
A Phase I/II Study of Lenalidomide and Obinutuzumab (GA101) in Relapsed Indolent Non-Hodgkin's Lymphoma
Study Overview
Status
Conditions
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Small Lymphocytic Lymphoma
- Refractory Small Lymphocytic Lymphoma
- Recurrent Follicular Lymphoma
- Refractory Follicular Lymphoma
- Refractory Marginal Zone Lymphoma
- Grade 3a Follicular Lymphoma
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of lenalidomide plus obinutuzumab in relapsed/refractory indolent lymphoma. (Phase I) II. To evaluate the safety of lenalidomide in combination with obinutuzumab in patients with relapsed/refractory indolent lymphoma. (Phase II) III. To determine the overall response rate (ORR) of the combination in patients with relapsed/refractory indolent lymphoma. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the complete response rate, time to progression (TTP), and progression free survival in patients with indolent lymphoma following treatment with obinutuzumab + lenalidomide.
II. To evaluate changes in immune effector cells and the tumor microenvironment following treatment with obinutuzumab + lenalidomide.
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
Patients receive lenalidomide orally (PO) once daily (QD) on days 2-22 and obinutuzumab intravenously (IV) over 4-5 hours on days 1, 2, 8, 15, and 22 of cycle 1 and on day 1 of each subsequent cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients not experiencing progression and who in the opinion of treating physician are deriving benefit from combination treatment may continue lenalidomide for an additional 6 cycles (up to cycle 12) and obinutuzumab on day 1 every 2 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 1 year, and then yearly thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- A diagnosis of small lymphocytic lymphoma, follicular lymphoma (grades 1-3a), or marginal zone lymphoma
- Evidence of progression or lack of response following at least 1 prior treatment for indolent lymphoma
- Able and willing to provide written informed consent and to comply with the study protocol
- Must have at least 1 node greater than 1.5 cm in short axis diameter
- Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; ANC < 1.5 x 10^9/L if cytopenia is due to extensive bone marrow involvement of disease as determined by the treating physician
- Platelet count (PLT) >= 75 x 10^9/L; PLT count less than 100 x 10^9/L if cytopenia is due to extensive bone marrow involvement of disease as determined by the treating physician
- For men who are not surgically sterile, agreement to use a barrier method of contraception for >= 3 months after the last obinutuzumab dose; in addition, male patients must agree to request that their partners use an additional method of contraception, such as oral contraceptives, intrauterine device, barrier method of contraception, or spermicidal jelly
- For women of reproductive potential who are not surgically sterile, agreement to use two adequate methods of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly for >= 12 months after the last obinutuzumab dose
Females of childbearing potential (FCBP) must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy
- A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of Revlimid REMS program
- For patients with bulky disease (tumors > 5 cm); must be able to take aspirin (81 mg or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)
- Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program; able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
Exclusion Criteria:
- Evidence ongoing transformation into aggressive NHL
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- Known hypersensitivity to thalidomide or lenalidomide
- Regular treatment with corticosteroids during the 4 weeks prior to the start of cycle 1, unless administered for indications other than NHL at a dose equivalent to =< 30 mg/day prednisone
- History of prior malignancy within the last 5 years, with the exception of curatively treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma of the cervix
- Evidence or history of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association class III or IV cardiac disease, severe arrhythmia, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 4 weeks prior to the start of cycle 1; patients with suspected active or latent tuberculosis (latent tuberculosis needs to be confirmed by positive interferon-gamma release assay)
- Vaccination with live vaccines within 28 days prior to start of treatment
- Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma)
- Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance normal), or calculated creatinine clearance < 40 mL/min (using Cockcroft-Gault formula)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Total bilirubin > 1.5 x ULN (or > 3 x ULN for patients with documented Gilbert syndrome)
- Any history of hepatitis B infection
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing); patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
- Known history of human immunodeficiency virus (HIV) seropositive status
- Positive test results for human T-lymphotropic 1 (HTLV 1) virus; HTLV testing is required in patients from endemic countries (Japan, countries in the Caribbean basin, South America, Central America, Sub Saharan Africa, and Melanesia)
- Pregnant or lactating
- Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
- Participation in another clinical trial with drug intervention within 21 days prior to start of cycle 1 and during the study
- Patients with small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) are excluded during the phase I portion of the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (lenalidomide, obinutuzumab)
Patients receive lenalidomide PO QD on days on days 2-22 and obinutuzumab IV over 4-5 hours on days 1, 2, 8, 15, and 22 of cycle 1 and on day 1 of each subsequent cycle.
Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients not experiencing progression and who in the opinion of treating physician are deriving benefit from combination treatment may continue lenalidomide for an additional 6 cycles (up to cycle 12) and obinutuzumab on day 1 every 2 months for up to 2 years in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Given PO
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose of lenalidomide when given with obinutuzumab defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT) (Phase I)
Time Frame: 28 days
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Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4. Toxicity type and severity by dose level will be summarized using frequency tables.
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28 days
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Incidence of DLTs after course 1 assessed using NCI CTCAE version 4 (Phase II)
Time Frame: After 28 days (1 course)
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Toxicity type and severity will be summarized for each patient cohort using frequency tables.
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After 28 days (1 course)
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Overall response rate (complete response + partial response) (Phase II)
Time Frame: After 168 days (6 courses)
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The overall response rate for each patient cohort will be calculated and the Clopper Pearson confidence interval will be provided.
Chi square test or Fisher's exact test will be used to evaluate the association between patient prognostic factor and response.
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After 168 days (6 courses)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 4 years
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The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
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Up to 4 years
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Progression-free survival
Time Frame: Up to 4 years
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The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier.
Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
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Up to 4 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Loretta Nastoupil, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Lymphoma, B-Cell
- Chronic Disease
- Lymphoma
- Lymphoma, Follicular
- Recurrence
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell, Marginal Zone
- Leukemia, Lymphocytic, Chronic, B-Cell
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Lenalidomide
- Obinutuzumab
Other Study ID Numbers
- 2013-0261 (Other Identifier: M D Anderson Cancer Center)
- NCI-2014-00943 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- ML28301
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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