Rituximab With or Without Lenalidomide in Treating Patients With Previously Untreated Follicular Lymphoma

NCT ID: NCT01307605

Last Updated: 2023-06-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-09
• Study Completion Date: 2023-01-25

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Lenalidomide may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. It is not yet known whether rituximab is more effective when given alone or together with lenalidomide in treating patients with follicular lymphoma.

PURPOSE: This randomized phase II trial is studying rituximab to see how well it works compared with giving rituximab together with lenalidomide in treating patients with previously untreated follicular lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To determine the activity of rituximab in combination with lenalidomide versus rituximab alone in patients with previously untreated follicular lymphoma in need of therapy.

Secondary

• To determine the safety of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to grade of disease (grades 1 or 2 vs 3a), presence of bulky disease (defined as masses ≥ 6 cm) (yes vs no), Follicular Lymphoma International Prognostic Index score (1 or 2 vs ≥ 3), and participating centers. Patients are randomized to 1 of 2 treatment arms.

• Arm A: Patients receive rituximab IV on day 1 in weeks 1, 2, 3, 4 and weeks 12, 13, 14, 15 in the absence of disease progression or unacceptable toxicity.
• Arm B: Patients receive rituximab IV as in arm A. Patients also receive oral lenalidomide once daily, starting 14 days before first rituximab administration and last until 14 days after the last rituximab administration, in the absence of disease progression or unacceptable toxicity.

All patients undergo restaging at week 10. Patients who show less than a minimal response (i.e., reduction of more than 25% in sum of product of diameters [SPD]) are off study treatment and transferred to the follow-up phase. Patients undergo a second restaging in week 23.

Some patients may undergo biopsies and blood and bone marrow sample collection periodically for biomarker studies.

After completion of study treatment, patients are followed up periodically for 20 years.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab

Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: BIOLOGICAL

Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters

Rituximab plus Lenalidomide

Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.

Group Type: ACTIVE_COMPARATOR

lenalidomide

Intervention Type: DRUG

Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.

Interventions

Rituximab

Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters

Intervention Type: BIOLOGICAL

lenalidomide

Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.

Intervention Type: DRUG

Other Intervention Names

Rituximab (MabThera); Lenalidomide (Revlimid)

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular lymphoma

• Stage III or IV disease OR stage II disease not suitable for radiotherapy
• Grades 1, 2, or 3a disease
• Previously untreated disease
• CD20-positive disease
• Patients in need of systemic therapy, meeting at least 1 of the following criteria:

• Symptomatic enlarged lymph nodes, spleen, or other lymphoma manifestations
• Bulky disease ≥ 6 cm in long diameter
• Clinically significant progression over at least 6 months of any tumor lesion
• Anemia (hemoglobin < 100 g/L) or thrombocytopenia (platelet count < 100 x 10^9/L) due to lymphoma
• Clinically significant progressive decrease in hemoglobin or platelet count due to lymphoma
• B-symptoms, weight loss > 10% within the past 6 months, drenching night sweats, or fever > 38°C not due to infection
• At least one two-dimensionally measurable lesion with longest transverse diameter > 10 mm
• Paraffin-embedded tumor tissue available
• No known CNS involvement

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• EF ≥ 50% for patients with a history of cardiac disease or older than 70 years
• Neutrophil count ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to Gilbert syndrome)
• ALT ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Creatinine clearance ≥ 30 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception 4 weeks prior to, during, and for 12 months after completion of study therapy
• Must be compliant and geographically proximal to allow for proper staging and follow-up
• No serious underlying medical condition, at the judgment of the investigator, which could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
• No malignancy within the past 3 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
• No psychiatric disorder precluding understanding information of trial-related topics, giving informed consent, or interfering with compliance for oral drug intake
• No known hypersensitivity to trial drugs or hypersensitivity to any other components of the trial drugs
• No known HIV positivity or hepatitis C infection
• No serological evidence of current or past hepatitis B infection, unless the serological findings are clearly due to vaccination

PRIOR CONCURRENT THERAPY:

• No prior systemic therapy for this disease
• At least 3 months since prior radiotherapy
• At least 30 days since prior treatment in another clinical trial
• At least 4 weeks since prior and no concurrent corticosteroids unless administered as prophylaxis in at-risk patients for ≤ 3 days or at a dose equivalent to prednisone ≤ 15 mg/day, for indications other than lymphoma or lymphoma-related symptoms
• No concomitant drugs contraindicated for use with the trial drugs
• No other concurrent experimental drugs or anticancer therapy
• No other concurrent investigational treatments

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swiss Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emanuele Zucca, MD

Role: STUDY_CHAIR

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Eva K. Kimby, MD, PhD

Role: STUDY_CHAIR

Karolinska Institutet

Felicitas Hitz, MD

Role: PRINCIPAL_INVESTIGATOR

Cantonal Hospital of St. Gallen

Bjorn Ostenstad, MD

Role: PRINCIPAL_INVESTIGATOR

Ullevaal University Hospital

Locations

Haukeland Hospital - University of Bergen

Bergen, , Norway

Sorlandet Sykehus HF Kristiansand

Kristiansand, , Norway

Ullevaal University Hospital

Oslo, , Norway

Helse Stavanger HF

Stavanger, , Norway

University Hospital of North Norway - Tromso

Tromsø, , Norway

St. Olavs University Hospital

Trondheim, , Norway

Sahlgrenska University Hospital

Gothenburg, , Sweden

University Hospital of Linkoping

Linköping, , Sweden

Sunderbyn Hospital

Luleå, , Sweden

Lund University Hospital

Lund, , Sweden

Karolinska University Hospital - Huddinge

Stockholm, , Sweden

Karolinska University Hospital - Solna

Stockholm, , Sweden

Sundsvall Hospital

Sundsvall, , Sweden

Norrlands University Hospital

Umeå, , Sweden

Uppsala University Hospital

Uppsala, , Sweden

Kantonsspital Aarau

Aarau, , Switzerland

Kantonsspital Baden

Baden, , Switzerland

Saint Claraspital AG

Basel, , Switzerland

Universitaetsspital-Basel

Basel, , Switzerland

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, , Switzerland

Inselspital Bern

Bern, , Switzerland

Spitalzentrum Oberwallis - Brig

Brig, , Switzerland

Kantonsspital Bruderholz

Bruderholz, , Switzerland

Kantonsspital Graubuenden

Chur, , Switzerland

University Hospital

Geneva, , Switzerland

Kantonsspital Liestal

Liestal, , Switzerland

Kantonsspital Olten

Olten, , Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Regionalspital

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Klinik Hirslanden

Zurich, , Switzerland

City Hospital Triemli

Zurich, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Countries

Norway; Sweden; Switzerland

References

Menter T, Tzankov A, Zucca E, Kimby E, Hultdin M, Sundstrom C, Beiske K, Cogliatti S, Banz Y, Cathomas G, Karjalainen-Lindsberg ML, Grobholz R, Mazzucchelli L, Sander B, Hawle H, Hayoz S, Dirnhofer S. Prognostic implications of the microenvironment for follicular lymphoma under immunomodulation therapy. Br J Haematol. 2020 May;189(4):707-717. doi: 10.1111/bjh.16414. Epub 2020 Feb 3.

Reference Type: DERIVED

PMID: 32012230 (View on PubMed)

Zucca E, Rondeau S, Vanazzi A, Ostenstad B, Mey UJM, Rauch D, Wahlin BE, Hitz F, Hernberg M, Johansson AS, de Nully Brown P, Hagberg H, Ferreri AJM, Lohri A, Novak U, Zander T, Bersvendsen H, Bargetzi M, Mingrone W, Krasniqi F, Dirnhofer S, Hayoz S, Hawle H, Vilei SB, Ghielmini M, Kimby E; Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood. 2019 Jul 25;134(4):353-362. doi: 10.1182/blood-2018-10-879643. Epub 2019 May 17.

Reference Type: DERIVED

PMID: 31101627 (View on PubMed)

Other Identifiers

SWS-SAKK-35-10

Identifier Type: -

Identifier Source: secondary_id

2010-021253-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CELGENE-SWS-SAKK-35/10

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SAKK 35/10

Identifier Type: -

Identifier Source: org_study_id