Clinical trial NCT02285062: Efficacy and Safety Study of Lenalidomide Plus R-CHOP Chemotherapy Versus Placebo Plus R-CHOP Chemotherapy in Untreated ABC Type Diffuse Large B-cell Lymphoma
Official title: Phase 3 Randomized, Double-Blind, Placebo Controlled, Multicenter Study to Compare the Efficacy and Safety of Lenalidomide (CC-5013) Plus R-CHOP Chemotherapy (R2-CHOP) Versus Placebo Plus R-CHOP Chemotherapy in Subjects With Previously Untreated Activated B-cell Type Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Large B-Cell, Diffuse
Keywords: R-CHOP chemotherapy
DLBCL front line therapy
gene expression profiling (GEP) activated B-cell (ABC) type DLBCL biomarkers
Activated B-Cell (ABC) type
Diffuse Large B-Cell Lymphoma, not otherwise specified
Diffuse Large B-Cell Lymphoma, associated with chronic inflammation
Diffuse Large B-Cell Lymphoma, Epstein-Barr virus positive (EBS+) of the elderly
Diffuse Large B-Cell Lymphoma, T-cell / histiocyte-rich
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2014-11-06
Enrollment: 570
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of lenalidomide, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R2-CHOP) chemotherapy versus placebo, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (placebo-R-CHOP) chemotherapy in patients who have previously untreated ABC type DLBCL.

Detailed description: This research study is for patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL) of the activated B-cell (ABC) type who have not yet been treated. DLBCL is a cancer of a type of blood cell called B-lymphocytes. B lymphocytes are part of the body's immune system. There are different types of DLBCL. About a third of newly diagnosed DLBCL cancers are the ABC type. It has been observed that treatment does not work as well for patients with the ABC type compared to patients with other DLBCL types who receive standard treatment. However, at this time both ABC type and other DLBCL type patients receive the same standard treatments.

Patients with DLBCL who are otherwise healthy are usually treated first with the chemotherapy drug combination called R-CHOP. The drugs in this combination are "R" for rituximab, "C" for cyclophosphamide, "H" for doxorubicin which has a chemical name of hydroxydaunomycin, "O" for vincristine which has a trade name of oncovin, and "P" for prednisone. Depending on the local practice where you are treated, R-CHOP may be given for 6 or 8 cycles. A cycle could lasts for 14 or 21 days. The R-CHOP drug combination is approved for the treatment of DLBCL of all types, including ABC type. R-CHOP is standard care.

This study will test the standard R-CHOP21 against R-CHOP21 plus lenalidomide. The purpose is to see whether adding lenalidomide works better and is as safe as R-CHOP by itself. This study is only for patients with ABC type DLBCL who have not yet been treated. Lenalidomide is not approved for use in DLBCL. Its use in this disease is experimental. In this study, the experimental treatment is lenalidomide + R-CHOP21 x 6.

This study will use a gene expression profile (GEP) test to see if a patient has the ABC type. The results of this GEP test affect whether you may be treated on this study. Because the performance of this test has not been proven, it is for investigational use only, and is still under development. This means the GEP test is an experimental test.

Eligibility criteria: Inclusion Criteria:

1. Histologically proven Diffuse Large B-Cell Lymphoma of the Activated B-Cell type
2. Newly diagnosed, previously untreated Diffuse Large B-Cell Lymphoma
3. Measurable Diffuse Large B-Cell Lymphoma disease by Computed Tomography (CT) / Magnetic Resonance Imagining (MRI) scans
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
5. Age 18 - 80 years; age \> 80 allowed at investigator discretion if performance status ≤ 1; and each organ system score ≤ 2 using cumulative illness rating scale (CIRS)

Exclusion Criteria:

1. Diagnosis of lymphoma histologies other than Diffuse Large B-Cell Lymphoma
2. History of malignancies, other than Diffuse Large B-Cell Lymphoma, unless the patient has been disease free for 5 years or more
3. Known seropositive for, or history of, active Human Immunodeficiency Virus (HIV) Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
4. Contraindication to any drug in the chemotherapy regimen, and specifically: LVEF (Left Ventricular Ejection Fraction) \< 45% or peripheral neuropathy grade 2

Primary outcomes:
measure: Kaplan-Meier Estimate of Progression Free Survival (PFS)
timeFrame: From the date of randomization up to the data cut off date of 15 March 2019; median follow-up of 24.5 months
Secondary outcomes:
measure: Kaplan-Meier (K-M) Estimate of Event Free Survival (EFS)
timeFrame: From the date of randomization up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
measure: K-M Estimate of Overall Survival (OS)
timeFrame: From randomization until death due to any cause (up to approximately 86 months)
measure: Percentage of Participants Who Achieved a Complete Response (CR)
timeFrame: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
measure: Percentage of Participants Who Achieved an Objective Response
timeFrame: From randomization date up to the data cut off date of 15 March 2019; median total treatment duration was 18.10 weeks for both treatment arms; range = 1.6 to 29.0 weeks for R2-CHOP arm and 0.3 to 22.9 weeks for placebo-R-CHOP arm
measure: K-M Estimate of Duration of Complete Response
timeFrame: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months.
measure: K-M Estimate of Time to Next Lymphoma Therapy (TTNLT)
timeFrame: From randomization date up to the data cut off date of 15 March 2019; median follow-up was 24.5 months
measure: Percentage of Participants Who Completed the Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Questionnaire
timeFrame: Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Percentage of Participants Who Completed the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Health Related Quality of Life (HR-QoL) Questionnaire
timeFrame: Screening, Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the FACT-Lym Physical Well-Being Subscale
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the FACT-Lym Additional Concerns Subscale
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the FACT-Lym Functional Well-Being Subscale
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the FACT-Lym Trial Outcome Index (TOI)
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the Euroqol 5-Dimension 3-Level (EQ-5D-3L) Index Score
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
measure: Mean Change From Baseline in the EQ-5D-3L Visual Analogue Scale (VAS)
timeFrame: Baseline and Midcycle = after Cycle 3 but before Cycle 4, Cycle 6 Day 1 (C6D1), End of Treatment (C6,D21), and Follow-Up Period up to Week 34
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Local Institution - 177
state: Arkansas
city: Orange
country: United States
facility: Local Institution - 136
state: California
city: Sacramento
country: United States
facility: Local Institution - 127
state: California
city: New Haven
country: United States
facility: Local Institution - 169
state: Connecticut
city: Hollywood
country: United States
facility: Local Institution - 128
state: Florida
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Fairway
country: United States
facility: Local Institution - 143
state: Kansas
city: Shreveport
country: United States
facility: Local Institution - 158
state: Louisiana
city: Bethesda
country: United States
facility: Center For Cancer And Blood Disorders
state: Maryland
city: Minneapolis
country: United States
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state: Minnesota
city: Minneapolis
country: United States
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state: Minnesota
city: Rochester
country: United States
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state: Minnesota
city: Durham
country: United States
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state: North Carolina
city: Philadelphia
country: United States
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state: Pennsylvania
city: Dallas
country: United States
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state: Texas
city: Dallas
country: United States
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state: Texas
city: Salt Lake City
country: United States
facility: Local Institution - 146
state: Utah
city: Edmonds
country: United States
facility: Local Institution - 905
state: Washington
city: Issaquah
country: United States
facility: Local Institution - 903
state: Washington
city: Seattle
country: United States
facility: Local Institution - 162
state: Washington
city: Seattle
country: United States
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state: Washington
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state: New South Wales
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state: Victoria
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state: Victoria
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facility: Local Institution - 301
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country: Belgium
facility: Local Institution - 307
city: Roeselare
country: Belgium
facility: Local Institution - 305
city: Sint-Niklaas
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facility: Local Institution - 303
city: Calgary
country: Canada
facility: Local Institution - 368
state: Alberta
city: Surrey
country: Canada
facility: Local Institution - 373
state: British Columbia
city: Saint John
country: Canada
facility: Local Institution - 366
state: New Brunswick
city: Greenfield Park
country: Canada
facility: Local Institution - 362
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 365
state: Quebec
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country: China
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country: China
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country: China
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country: Italy
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Korea, Republic of
facility: Local Institution - 830
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country: Korea, Republic of
facility: Local Institution - 826
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country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Local Institution - 828
city: Amsterdam
country: Netherlands
facility: Local Institution - 358
city: Breda
country: Netherlands
facility: Local Institution - 359
city: Hoofddorp
country: Netherlands
facility: Local Institution - 357
city: Leeuwarden
country: Netherlands
facility: Local Institution - 354
city: s-Hertogenbosch
country: Netherlands
facility: Local Institution - 353
city: Schiedam
country: Netherlands
facility: Local Institution - 350
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country: New Zealand
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city: Palmerston
country: New Zealand
facility: Local Institution - 243
city: Figueira da Foz
country: Portugal
facility: Local Institution - 730
city: Lisboa
country: Portugal
facility: Local Institution - 732
city: Lisboa
country: Portugal
facility: Local Institution - 729
city: Pragal
country: Portugal
facility: Local Institution - 727
city: San Juan
country: Puerto Rico
facility: Local Institution - 115
city: Kazan
country: Russian Federation
facility: Local Institution - 050
city: Moscow
country: Russian Federation
facility: Local Institution - 052
city: St. Petersburg
country: Russian Federation
facility: Local Institution - 051
city: Barcelona
country: Spain
facility: Local Institution - 776
city: Barcelona
country: Spain
facility: Local Institution - 780
city: Caceres
country: Spain
facility: Local Institution - 796
city: Madrid
country: Spain
facility: Local Institution - 783
city: Madrid
country: Spain
facility: Local Institution - 785
city: Madrid
country: Spain
facility: Local Institution - 787
city: Madrid
country: Spain
facility: Local Institution - 788
city: Salamanca
country: Spain
facility: Local Institution - 797
city: Sevilla
country: Spain
facility: Local Institution - 790
city: Sevilla
country: Spain
facility: Local Institution - 800
city: Valencia
country: Spain
facility: Local Institution - 793
city: Valencia
country: Spain
facility: Local Institution - 802
city: Bellinzona
country: Switzerland
facility: Local Institution - 323
city: Geneva
country: Switzerland
facility: Local Institution - 320
city: Winterthur
country: Switzerland
facility: Local Institution - 321
city: Niao-Sung Hsiang Kaohsiung County
country: Taiwan
facility: Local Institution - 253
city: Taichung City
country: Taiwan
facility: Local Institution - 255
city: Taipei, Zhongzheng Dist.
country: Taiwan
facility: Local Institution - 252
city: Adana
country: Turkey
facility: Local Institution - 429
city: Ankara
country: Turkey
facility: Local Institution - 431
city: Antalya
country: Turkey
facility: Local Institution - 430
city: Denizli
country: Turkey
facility: Local Institution - 435
city: Edirne
country: Turkey
facility: Local Institution - 428
city: Istanbul
country: Turkey
facility: Local Institution - 432
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Nowakowski GS, Chiappella A, Witzig TE, Spina M, Gascoyne RD, Zhang L, Flament J, Repici J, Vitolo U. ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma. Future Oncol. 2016 Jul;12(13):1553-63. doi: 10.2217/fon-2016-0130. Epub 2016 Apr 18.
citation: Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, Ozcan M, Hong X, Zhu J, Jin J, Belada D, Bergua JM, Piazza F, Mocikova H, Molinari AL, Yoon DH, Cavallo F, Tani M, Yamamoto K, Izutsu K, Kato K, Czuczman M, Hersey S, Kilcoyne A, Russo J, Hudak K, Zhang J, Wade S, Witzig TE, Vitolo U. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2021 Apr 20;39(12):1317-1328. doi: 10.1200/JCO.20.01366. Epub 2021 Feb 23.