NCT01938001 · CITED IN SOURCE DOCUMENTS

Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2023-02-22

This double-blind randomized, parallel group study will evaluate the efficacy and safety of lenalidomide (Revlimid, CC-5013) in combination with rituximab (MabThera/Rituxan) in patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma. Patients will be randomized to receive either lenalidomide or placebo for twelve 28-day cycles in combination with rituximab. Anticipated time on study treatment is 1 year.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)

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outcome · POSTED

Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Kaplan-Meier Estimate of Overall Survival (OS)

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outcome · POSTED

Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC

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outcome · POSTED

Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)

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outcome · POSTED

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Age ≥18 years at the time of signing the informed consent document. * Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. * Histologically confirmed marginal zone lymphoma or follicular lymphoma (grade 1, 2 or 3a; CD20+ by flow cytometry or histochemistry). * Previously treated with at least one prior systemic chemotherapy, immunotherapy or chemoimmunotherapy and have received at least 2 previous doses of rituximab. * Documented relapsed, refractory or progressive disease after treatment with systemic therapy and must not be rituximab-refractory. * Investigator considers rituximab monotherapy appropriate. * Bi-dimensionally measurable disease on cross sectional imaging by X-ray computed tomography (CT) or magnetic resonance imaging (MRI). * Need of treatment for relapsed, progressed or refractory disease as assessed by the investigator. * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Adequate bone marrow function. * Willingness to follow study visit schedule, pregnancy precautions and other protocol requirements. Exclusion Criteria: * Histology other than follicular or marginal zone lymphoma or clinical evidence of transformation or Grade 3b follicular lymphoma. * Subjects taking corticosteroids during the last week prior to study treatment, unless administered at a dose equivalent to \< 20 mg/day prednisone or prednisolone. * Systemic anti-lymphoma therapy within 28 days or use of antibody agents within 8 weeks use of radioimmunotherapy within 6 months. * Known seropositive for or active viral infection with hepatitis B virus (HBV) or/and human immunodeficiency virus (HIV). * Known hepatitis C virus (HCV) positive with chronic HCV or active viral infection with HCV hepatitis requiring anti-viral medication (at time of randomization). * Life expectancy \< 6 months. * Known sensitivity or allergy to murine products. * Prior history of malignancies, other than follicular or marginal zone lymphoma, unless the subject has been free of the disease for ≥ 5 years. * Prior use of lenalidomide. * Known allergy to thalidomide. * Neuropathy \> Grade 1. * Presence or history of central nervous system involvement by lymphoma. * Subjects who are at a risk for a thromboembolic event and are not willing to take prophylaxis for it. * Uncontrolled intercurrent illness. * Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document. * Pregnant or lactating females. * Any condition that places the subject at unacceptable risk if he/she were to participate in the study or that confounds the ability to interpret data from the study.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received rituximab 375 mg/m\^2 intravenously (IV) every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from Cycles 2 to 5 plus lenalidomide 20 mg by mouth (PO) once daily on Days 1 to 21 every 28 days, up to 12 cycles (21-day treatment and 7-day rest period); if creatinine clearance (CrCl) was ≥ 30 mL/min but \< 60 mL/min, participants received lenalidomide 10 mg capsules on days 1 to 21 every 28 days.
intervention Names
Drug: Rituximab
Drug: Lenalidomide
label
Rituximab and Lenalidomide
type
EXPERIMENTAL
description
Participants received riituximab 375 mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) and on Day 1 of every 28-day cycle from cycle 2 to 5 plus placebo (identically matched capsule) once daily on Days 1 to 21 of every 28-day cycle up, to 12 cycles.
intervention Names
Drug: Rituximab
Drug: Placebo
label
Rituximab and Placebo
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Rituximab and Lenalidomide
Rituximab and Placebo
description
Rituximab 375mg/m\^2 IV every week in Cycle 1 (Days 1, 8, 15 and 22) on Day 1 of every 28 day cycle from Cycles 2 to 5
name
Rituximab
other Names
Rituxan
type
DRUG
arm Group Labels
Rituximab and Lenalidomide
description
Lenalidomide 20mg by mouth (PO) daily on Days 1 to 21 every 28 days up to 12 cycles
name
Lenalidomide
other Names
CC-5013, Revlimid
type
DRUG
arm Group Labels
Rituximab and Placebo
description
Placebo (identical matched capsule) PO daily on Days 1 to 21 every 28 days
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: QUADRUPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR
OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 358
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression-free survival (PFS) was defined as the time from date of randomization into the study to the first observation of documented disease progression or death due to any cause, whichever occurred first. PFS was based on the data from the IRC review using the modified 2007 International Working Group Response Criteria (IWGRC) using FDA censoring rules.
measure
Kaplan Meier Estimate of Progression Free Survival Assessed by the Independent Review Committee (IRC) According to the 2007 International Working Group Response Criteria (IWGRC)
time Frame
From randomization of study drug up to disease progression or death, which occurred first; up to the data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).

secondary Outcomes

description
DCCR was defined as the percentage of participants with a best response of complete response (CR) that lasted no less than one year (≥ 48 weeks) during the study prior to administration of new anti-lymphoma therapy. A CR is defined as a complete disappearance of any disease-related symptoms and normalization of biochemical abnormalities.
measure
Durable Complete Response Rate (DCCR) as Assessed by the IRC According to the 2007 IWGRC
time Frame
From first dose of investigational product (IP) to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomiade arm and 11.04 months in the rituximab/placebo arm
description
Overall survival was defined as the time from randomization to death from any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for participants who were lost to follow-up before death was documented.
measure
Kaplan-Meier Estimate of Overall Survival (OS)
time Frame
From date of randomization to death due to any cause (Average of 55.71 months and a maximum up to 95.2 months)
description
Percentage of participants with an objective response is defined as having a response of at least a PR during the study without administration of new anti-lymphoma therapy. A complete response = a complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities; a partial response (PR) = 50% decrease in SPD of the 6 largest dominant nodes or nodal masses. No increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD.
measure
Percentage of Participants With an Objective Response as Assessed by the IRC According to the 2007 IWGRC
time Frame
From date of first dose to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
description
Percentage of participants with a best response of at CR during the study without administration of new anti-lymphoma therapy. A CR = Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of any disease-related symptoms, and normalization of biochemical abnormalities.
measure
Percentage of Participants With a Best Response of Complete Response as Assessed by the IRC According to the 2007 IWGRC
time Frame
From date of first dose up to data cut-off date of 22 June 2018; the median treatment duration was 11.19 months in the rituximab/lenalidomide arm and 11.04 months in the rituximab/placebo arm
description
Duration of response (DOR) was defined as the time from initial response (at least PR) until documented progressive disease (PD) or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.
measure
Kaplan-Meier Estimate of Duration of Objective Response as Assessed by the IRC According to the 2007 IWGRC
time Frame
From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
description
DOCR was defined as the time from initial CR until documented PD or death. Participants who had not progressed at the time of analysis were censored at the last assessment date that the participant was known to be progression free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participants was known to be progression free.
measure
Kaplan-Meier Estimate of Duration of Complete Response (DOCR) as Assessed by the IRC According to the 2007 IWGRC
time Frame
From randomization up to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
description
Event-free survival (EFS) was defined as the time from date of randomization to date of first documented progression, relapse, institution of new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy) or death from any cause. Responding participants and those who were lost to follow up were censored at their last tumor assessment date.
measure
Kaplan Meier Estimate of Event Free Survival as Assessed by the IRC According to the 2007 IWGRC
time Frame
From date of randomization to data cut-off date of 22 June 2018; overall median follow-up time for all participants was 28.30 months (range: 0.1 to 51.3 months).
description
Time to next anti-lymphoma treatment (TTNLT) was defined as the time from date of randomization to date of first documented administration of a new anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy or immunotherapy). The time to the next anti-lymphoma treatment was of special interest to the study.
measure
Kaplan Meier Estimate of Time to Next Anti-Lymphoma Treatment (TTNLT)
time Frame
From date of randomization to date of first documented administration of a new anti-lymphoma treatment (Average of 55.71 months and a maximum up to 95.2 months)
description
TEAEs include AEs that started or worsened between the date of the first dose and 28 days after the date of the last dose. A serious adverse event (SAE) is any: • Death; • Life-threatening event; • Any inpatient hospitalization or prolongation of existing hospitalization; • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect; • Any other important medical event. The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.03) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death
measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
time Frame
From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)

Full study description

brief Summary: This double-blind randomized, parallel group study will evaluate the efficacy and safety of lenalidomide (Revlimid, CC-5013) in combination with rituximab (MabThera/Rituxan) in patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma. Patients will be randomized to receive either lenalidomide or placebo for twelve 28-day cycles in combination with rituximab. Anticipated time on study treatment is 1 year.
detailed Description: Indolent lymphoma is a slow growing but incurable lymphoma which includes follicular lymphoma and marginal zone lymphoma. Follicular lymphoma and marginal zone lymphoma are cancers of the B lymphocyte, a type of white blood cell. Lenalidomide is an immunomodulatory drug (a drug that affects the immune system) which alters the body's immune system and it may also interfere with the development of tiny blood vessels involved in tumor growth. Therefore, lenalidomide may reduce or prevent the growth of cancer cells. Lenalidomide has also been shown to restore the immune cells' ability to attack and kill tumor cells, an ability that may be inhibited by follicular lymphoma and other lymphomas. The combination of rituximab and lenalidomide may eliminate the cancer while restoring the immune system's ability to attack tumor cells.

Source references

references

citation
Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML, Fruchart C, Libby EN, Casasnovas RO, Flinn IW, Haioun C, Maisonneuve H, Ysebaert L, Bartlett NL, Bouabdallah K, Brice P, Ribrag V, Daguindau N, Le Gouill S, Pica GM, Martin Garcia-Sancho A, Lopez-Guillermo A, Larouche JF, Ando K, Gomes da Silva M, Andre M, Zachee P, Sehn LH, Tobinai K, Cartron G, Liu D, Wang J, Xerri L, Salles GA; RELEVANCE Trial Investigators. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma. N Engl J Med. 2018 Sep 6;379(10):934-947. doi: 10.1056/NEJMoa1805104.
pmid
30184451
type
BACKGROUND
citation
Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabecadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. doi: 10.1200/JCO.19.00010. Epub 2019 Mar 21.
pmid
30897038
type
RESULT
citation
Leonard JP, Trneny M, Zhang H, Nowakowski GS, Izutsu K, Fowler N, Thieblemont C, Zinzani PL, Gkasiamis A, Ahn JR, Gribben JG; AUGMENT Trial Investigators. Lenalidomide Plus Rituximab for Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: 5-Year Follow-Up and Subgroup Analyses From the Phase III AUGMENT Trial. J Clin Oncol. 2026 Jun;44(16):1483-1489. doi: 10.1200/JCO-25-01770. Epub 2026 Apr 16.
pmid
41990300
type
DERIVED