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

NCT01307605 | Terminated Phase 2 DMC

• 4 other identifiers: SAKK 35/10SWS-SAKK-35-102010-021253-39CELGENE-SWS-SAKK-35/10
• Study Type: interventional
• Target: 154
• Locations: 3 countries
• Sites: 33

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.

Conditions

Lymphoma

Keywords

contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response (CR)

  The evaluation of CR is outlined in Appendix 1 Criteria for Evaluation of Response in Non-Hodgkin's Lymphoma.

  at week 23

Secondary Outcomes (6)

• Best overall response (OR)

  within 24 weeks

• Best Overall response (OR)

  within 12 weeks

• Progression-free survival

  until disease progression, for up to 10 years after randomization

• Time to first off-trial anti-lymphoma therapy

  until off-trial therapy administration, for up to 10 years after randomization

• Overall survival

  every 6 months for up to 10 years after randomization

Study Arms (2)

Rituximab

ACTIVE COMPARATOR

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

Biological: Rituximab

Rituximab plus Lenalidomide

ACTIVE COMPARATOR

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

Drug: lenalidomide

Interventions

Rituximab 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

Also known as: Rituximab (MabThera)

Rituximab

lenalidomide DRUG

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

Also known as: Lenalidomide (Revlimid)

Rituximab plus Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (33)

Haukeland Hospital - University of Bergen

Bergen, N-5021, Norway

Location

Sorlandet Sykehus HF Kristiansand

Kristiansand, 4604, Norway

Location

Ullevaal University Hospital

Oslo, 0424, Norway

Location

Helse Stavanger HF

Stavanger, 4068, Norway

Location

University Hospital of North Norway - Tromso

Tromsø, 9038, Norway

Location

St. Olavs University Hospital

Trondheim, 7006, Norway

Location

Sahlgrenska University Hospital

Gothenburg, S-413 45, Sweden

Location

University Hospital of Linkoping

Linköping, S-581 85, Sweden

Location

Sunderbyn Hospital

Luleå, 95128, Sweden

Location

Lund University Hospital

Lund, SE-22185, Sweden

Location

Karolinska University Hospital - Huddinge

Stockholm, S-141 86, Sweden

Location

Karolinska University Hospital - Solna

Stockholm, S-171 76, Sweden

Location

Sundsvall Hospital

Sundsvall, 85186, Sweden

Location

Norrlands University Hospital

Umeå, S-90185, Sweden

Location

Uppsala University Hospital

Uppsala, SE-75185, Sweden

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Baden

Baden, 5404, Switzerland

Location

Saint Claraspital AG

Basel, 4016, Switzerland

Location

Universitaetsspital-Basel

Basel, 4031, Switzerland

Location

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Spitalzentrum Oberwallis - Brig

Brig, 3900, Switzerland

Location

Kantonsspital Bruderholz

Bruderholz, 4101, Switzerland

Location

Kantonsspital Graubuenden

Chur, 7000, Switzerland

Location

University Hospital

Geneva, 1211, Switzerland

Location

Kantonsspital Liestal

Liestal, 4410, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Kantonsspital - St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Regionalspital

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Klinik Hirslanden

Zurich, 8032, Switzerland

Location

City Hospital Triemli

Zurich, 8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 32012230 DERIVED

• 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.

  PMID: 31101627 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular

Interventions

Rituximab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Emanuele Zucca, MD

  Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

  STUDY CHAIR

• Eva K. Kimby, MD, PhD

  Karolinska Institutet

  STUDY CHAIR

• Felicitas Hitz, MD

  Cantonal Hospital of St. Gallen

  PRINCIPAL INVESTIGATOR

• Bjorn Ostenstad, MD

  Ullevaal University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2011
• First Posted: March 3, 2011
• Study Start: February 9, 2011
• Primary Completion: June 20, 2014
• Study Completion: January 25, 2023
• Last Updated: June 27, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

NO (6); CH (18); SE (9)