CC-486, Lenalidomide, and Obinutuzumab for the Treatment of Recurrent or Refractory CD20 Positive B-cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT04578600|
Recruitment Status : Recruiting
First Posted : October 8, 2020
Last Update Posted : December 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Indolent B-Cell Non-Hodgkin Lymphoma Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Chronic Lymphocytic Leukemia Recurrent Mucosa-Associated Lymphoid Tissue Lymphoma Recurrent Follicular Lymphoma Recurrent Hairy Cell Leukemia Recurrent Lymphoplasmacytic Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Mucosa-Associated Lymphoid Tissue Lymphoma Refractory Follicular Lymphoma Refractory Hairy Cell Leukemia Refractory Lymphoplasmacytic Lymphoma Refractory Mantle Cell Lymphoma Refractory Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Refractory Small Lymphocytic Lymphoma||Drug: Lenalidomide Biological: Obinutuzumab Drug: Oral Azacitidine||Phase 1|
To assess the safety and toxicity of oral azacitidine (CC-486) in combination with lenalidomide and obinutuzumab.
I. To evaluate the efficacy of CC-486 in combination with lenalidomide and obinutuzumab in subjects with relapsed/refractory indolent B-cell lymphoma as assessed by:
Ia. Overall response rate: complete response (CR) + partial response (PR) per 2016 Lugano criteria and Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) criteria.
Ib. Duration of response (DOR): will be calculated from time of initial response assessment demonstrating at least PR until disease response assessment that demonstrates progressive disease.
Ic. Time to response (TTR): calculated as time from registration to first disease response assessment that demonstrates at least PR.
Id. Progression-free survival (PFS): Patients are considered a failure for this endpoint if they die or if they relapse/progress or receive additional anti-lymphoma therapy.
Ie. Determine the recommended phase 2 dose (RP2D).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/IB Pilot Study of CC-486 Combined With Lenalidomide and Obinutuzumab for Relapsed/Refractory Indolent B-Cell Lymphoma|
|Actual Study Start Date :||October 23, 2020|
|Estimated Primary Completion Date :||October 1, 2022|
|Estimated Study Completion Date :||April 1, 2023|
Experimental: Treatment (lenalidomide, oral azacitidine, obinutuzumab)
Patients receive azacitidine PO QD on days 1-21, obinutuzumab IV over on days 8, 15, 22, and 29, and lenalidomide PO QD on days 8-28 of cycle 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity. Patients then receive azacitidine PO QD on days 1-21, obinutuzumab IV over on day 1, and lenalidomide PO QD on days 1-21. Cycles repeats every 28 days in the absence of disease progression, unacceptable toxicity, or until stem cell transplant. Patients who achieve SD, PR, or CR do not proceed to stem cell transplant may continue treatment for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Oral Azacitidine
Other Name: CC-486
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days post-last dose ]Safety summaries will include tabulations in the form of tables and listings. The frequency (number and percentage) of treatment-emergent AEs will be reported. The frequency of treatment-emergent AEs requiring discontinuation of study drug or dose reductions will be reported. Additional AE summaries will include AE frequency by AE severity and by relationship to study drug. Toxicity data by type and severity will be summarized by frequency tables. Per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.
- Complete response rate [ Time Frame: At 48 weeks ]Response will be assessed based on Cheson, Lugano classification 2016. The number and percentage of subjects with a complete response at 120 weeks will be tabulated.
- Overall response rate (ORR) (complete response + partial response) [ Time Frame: Up to 2 years ]Will be assessed by the investigator based on Cheson, Lugano classification 2016. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded.
- Duration of response [ Time Frame: From the time by which measurement criteria for complete response or partial response, whichever is recorded first, is met until death or the first date by which progressive disease is documented, assessed up to 2 years ]Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.
- Time to response [ Time Frame: From registration to first disease response assessment that demonstrates at least partial response, assessed up to 2 years ]Comparison by important subgroups will be made using the log-rank test. Will be estimated using the product-limit method of Kaplan and Meier.
- Progression-free survival [ Time Frame: From the date of first dose (cycle 1, day 1) to the date of first documented progression or death, assessed up to 2 years. ]Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.
- Recommended phase 2 dose [ Time Frame: Up to 35 days ]The maximum tolerated dose (MTD) will be defined as the highest dose of CC-486 tested in which fewer than 33% of patients experience a dose-limiting toxicity and at least 6 patients have been treated at that dose. The MTD will be the recommended phase 2 dose, provided that other safety considerations are acceptable.
- Time to next treatment [ Time Frame: From the end of cycle 24 (each cycle is 28 days) to the date of first documented new anti-lymphoma treatment, assessed up to 2 years. ]Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval. Comparison by important subgroups will be made using the log-rank test.
- Event-free survival [ Time Frame: From the date of first dose (cycle 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 2 years. ]
- Overall survival [ Time Frame: From the date of first dose (cycle 1, day 1) to the date of death regardless of cause, assessed up to years. ]
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): NCT04578600
|United States, California|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Joseph M. Tuscano 916-734-3771 firstname.lastname@example.org|
|Principal Investigator: Joseph M. Tuscano|
|Principal Investigator:||Joseph M Tuscano||University of California, Davis|