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 (ROBUST)

Celgene

Status and phase: Completed; Phase 3

Conditions: Lymphoma, Large B-Cell, Diffuse

Treatments: Drug: Rituximab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: vincristine; Drug: Placebo; Drug: lenalidomide; Drug: prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT02285062

CC-5013-DLC-002

2013-004054-21 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 570 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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570 participants in 2 patient groups

R2-CHOP

Experimental group

Description:

Lenalidomide plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

Treatment:

Drug: prednisone

Drug: Doxorubicin

Drug: Rituximab

Drug: vincristine

Drug: Cyclophosphamide

Drug: lenalidomide

R-CHOP

Active Comparator group

Description:

Placebo plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

Treatment:

Drug: prednisone

Drug: Doxorubicin

Drug: Rituximab

Drug: vincristine

Drug: Cyclophosphamide

Drug: Placebo