A Phase I/II Study of Lenalidomide and Obinutuzumab (GA101) in Relapsed Indolent Non-Hodgkin's Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Grade 3a Follicular Lymphoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose of Lenalidomide When Given With Obinutuzumab Defined as the Highest Dose Level Have Been Treated With Less Than 2 Instances of Dose Limiting Toxicity DLT.
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This phase I/II trial studies the side effects and best dose of lenalidomide when given together with obinutuzumab and how well this combination works in treating patients with low-grade non-Hodgkin lymphoma (NHL) that has returned after a period of improvement (relapsed). Biological therapies, such as lenalidomide, may attack specific cancer cells and stop them from growing or kill them. Obinutuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as CD20 receptors. When obinutuzumab attaches to CD20 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Giving lenalidomide and obinutuzumab together may work better in treating NHL.
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.
Investigators
Eligibility Criteria
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
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)
Arms & Interventions
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Lenalidomide
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.
Intervention: Obinutuzumab
Outcomes
Primary Outcomes
Maximum Tolerated Dose of Lenalidomide When Given With Obinutuzumab Defined as the Highest Dose Level Have Been Treated With Less Than 2 Instances of Dose Limiting Toxicity DLT.
Time Frame: 28 days after 168 days (6 courses)
To determine the maximum tolerated dose of lenalidomide plus obinutuzumab in relapsed/refractory indolent lymphoma the 3 by 3 method was used. (Phase I) Doses of Lenalidomide to be used are 10mg, 15mg, 20mg in Phase 1.
Secondary Outcomes
- Overall Survival, Time to Progression, and Progression Free Survival (Phase II)(up to 4 years)