NCT01938001: AUGMENT

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

Completed Phase 3 Results posted Last updated 22 February 2023

What this trial tests

Phase 3 trial testing Rituximab in Lymphoma, Non-Hodgkin in 358 participants. Completed in 26 January 2022.

Timeline

21 November 2013

Primary endpoint
22 June 2018

26 January 2022

Quick facts

Lead sponsor	Celgene
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	358
Start date	21 November 2013
Primary completion	22 June 2018
Estimated completion	26 January 2022
Sites	160 locations across France, Italy, Japan, Russia, Belgium, United Kingdom, Germany, Israel

Drugs / interventions tested

• Rituximab — full drug profile →
• Lenalidomide — full drug profile →
• Placebo

Conditions studied

• Lymphoma, Non-Hodgkin — all drugs for Lymphoma, Non-Hodgkin →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Lymphoma, Non-Hodgkin. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	39.4	22.9 – NA
Rituximab + Placebo	14.1	11.4 – 16.7

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	25.3	19.1 – 32.3
Rituximab + Placebo	11.1	6.9 – 16.6

Kaplan-Meier Estimate of Overall Survival (OS) Secondary · From date of randomization to death due to any cause (Average of 55.71 months and a maximum up to 95.2 months)

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	NA	NA – NA
Rituximab + Placebo	NA	NA – NA

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

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

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	77.5	70.7 – 83.4
Rituximab + Placebo	53.3	45.8 – 60.8

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	33.7	26.8 – 41.2
Rituximab + Placebo	18.3	13.0 – 24.8

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	36.6	22.9 – NA
Rituximab + Placebo	21.7	12.8 – 27.6

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	NA	25.3 – NA
Rituximab + Placebo	NA	13.8 – NA

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	27.6	22.1 – NA
Rituximab + Placebo	13.9	11.4 – 16.7

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

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.

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	73.1	43.0 – NA
Rituximab + Placebo	31.8	22.2 – 39.4

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · From first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months)

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 underl

Any TEAE

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	174
Rituximab + Placebo	173

Any TEAE Related to Lenalidomide/Placebo (LEN/PBO)

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	159
Rituximab + Placebo	118

Any TEAE Related to Rituximab (RIT)

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	134
Rituximab + Placebo	105

Any Serious TEAE

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	45
Rituximab + Placebo	25

Any Serious TEAE Related to LEN/PBO

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	23
Rituximab + Placebo	8

Any Serious TEAE Related to RIT

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	13
Rituximab + Placebo	4

Any CTCAE Grade (GR) 3/4 TEAE

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	121
Rituximab + Placebo	58

Any CTCAE GR 3/4 TEAE Related to LEN/PBO

Group	Value	95% CI
Rituximab + Lenalidomide (R^2)	101
Rituximab + Placebo	38

Adverse events — posted to ClinicalTrials.gov

Time frame: Other (Not including Serious) Adverse Events (AEs) and Serious Adverse Events (SAEs) are collected from first dose to 28 days post last dose (Average of 55.71 months and a maximum up to 95.2 months). Participants were assessed for All-cause mortality from their date of randomization to study completion (Up to approximately 100 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rituximab + Lenalidomide (R^2)

Serious: 45/176 (26%)

Deaths: 27/178

Rituximab + Placebo

Serious: 25/180 (14%)

Deaths: 47/180

Serious adverse events (81 terms)

Reaction	System	Rituximab + Lenalidomide (…	Rituximab + Placebo
Pneumonia	Infections and infestations	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Sepsis	Infections and infestations	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Supraventricular tachycardia	Cardiac disorders	—	—
General physical health deterioration	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Syncope	Nervous system disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Pancytopenia	Blood and lymphatic system disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Arrhythmia	Cardiac disorders	—	—
Atrial flutter	Cardiac disorders	—	—
Cardiopulmonary failure	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Vertigo	Ear and labyrinth disorders	—	—

Other adverse events (55 terms — click to expand)

Reaction	System	Rituximab + Lenalidomide (…	Rituximab + Placebo
Neutropenia	Blood and lymphatic system disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Fatigue	General disorders	—	—
Leukopenia	Blood and lymphatic system disorders	—	—
Pyrexia	General disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Headache	Nervous system disorders	—	—
Asthenia	General disorders	—	—
Oedema peripheral	General disorders	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—
Nausea	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Influenza	Infections and infestations	—	—
White blood cell count decreased	Investigations	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Dizziness	Nervous system disorders	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—
Chills	General disorders	—	—
Pneumonia	Infections and infestations	—	—
Weight decreased	Investigations	—	—
Insomnia	Psychiatric disorders	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Malaise	General disorders	—	—
Sinusitis	Infections and infestations	—	—

Most-reported serious reactions: Pneumonia, Febrile neutropenia, Pulmonary embolism, Neutropenia, Pyrexia, Sepsis, Pleural effusion, Anaemia.

Data from ClinicalTrials.gov NCT01938001 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma.
   Leonard JP, Trneny M, Izutsu K, Fowler NH, et al · · 2019 · cited 309× · PMID 30897038 · DOI 10.1200/jco.19.00010
2. Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma.
   Gribben JG, Fowler N, Morschhauser F. · · 2015 · cited 231× · PMID 26195701 · DOI 10.1200/jco.2014.59.5363
3. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance).
   Leonard JP, Jung SH, Johnson J, Pitcher BN, et al · · 2015 · cited 145× · PMID 26304886 · DOI 10.1200/jco.2014.59.9258
4. Exosome-Based Smart Drug Delivery Tool for Cancer Theranostics.
   Kar R, Dhar R, Mukherjee S, Nag S, et al · · 2023 · cited 125× · PMID 36621949 · DOI 10.1021/acsbiomaterials.2c01329
5. Limitations in Clinical Trials Leading to Anticancer Drug Approvals by the US Food and Drug Administration.
   Hilal T, Gonzalez-Velez M, Prasad V. · · 2020 · cited 65× · PMID 32539071 · DOI 10.1001/jamainternmed.2020.2250
6. The landscape of new drugs in lymphoma.
   Younes A, Ansell S, Fowler N, Wilson W, et al · · 2017 · cited 59× · PMID 28031560 · DOI 10.1038/nrclinonc.2016.205
7. Follicular Lymphoma: Recent and Emerging Therapies, Treatment Strategies, and Remaining Unmet Needs.
   Matasar MJ, Luminari S, Barr PM, Barta SK, et al · · 2019 · cited 41× · PMID 31346132 · DOI 10.1634/theoncologist.2019-0138
8. Lenalidomide plus rituximab (R² ) in previously untreated marginal zone lymphoma: subgroup analysis and long-term follow-up of an open-label phase 2 trial.
   Becnel MR, Nastoupil LJ, Samaniego F, Davis RE, et al · · 2019 · cited 41× · PMID 30919940 · DOI 10.1111/bjh.15843