Clinical trial NCT01307605: Rituximab With or Without Lenalidomide in Treating Patients With Previously Untreated Follicular Lymphoma
Official title: Rituximab Plus Lenalidomide or Rituximab Monotherapy for Untreated Patients With Follicular Lymphoma in Need of Therapy. A Randomized, Open-Label, Multicenter Phase II Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2011-03-03
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Complete response (CR)
timeFrame: at week 23
Secondary outcomes:
measure: Best overall response (OR)
timeFrame: within 24 weeks
measure: Best Overall response (OR)
timeFrame: within 12 weeks
measure: Progression-free survival
timeFrame: until disease progression, for up to 10 years after randomization
measure: Time to first off-trial anti-lymphoma therapy
timeFrame: until off-trial therapy administration, for up to 10 years after randomization
measure: Overall survival
timeFrame: every 6 months for up to 10 years after randomization
measure: Adverse events, including laboratory abnormality assessments and vital signs
timeFrame: from inclusion until 30 days after treatment discontinuation
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland Hospital - University of Bergen
city: Kristiansand
country: Norway
facility: Sorlandet Sykehus HF Kristiansand
city: Oslo
country: Norway
facility: Ullevaal University Hospital
city: Stavanger
country: Norway
facility: Helse Stavanger HF
city: Tromso
country: Norway
facility: University Hospital of North Norway - Tromso
city: Trondheim
country: Norway
facility: St. Olavs University Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linkoping
country: Sweden
facility: University Hospital of Linkoping
city: Lulea
country: Sweden
facility: Sunderbyn Hospital
city: Lund
country: Sweden
facility: Lund University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Huddinge
city: Stockholm
country: Sweden
facility: Karolinska University Hospital - Solna
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital
city: Umea
country: Sweden
facility: Norrlands University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Saint Claraspital AG
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Brig
country: Switzerland
facility: Spitalzentrum Oberwallis - Brig
city: Bruderholz
country: Switzerland
facility: Kantonsspital Bruderholz
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Geneva
country: Switzerland
facility: University Hospital
city: Liestal
country: Switzerland
facility: Kantonsspital Liestal
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Kantonsspital - St. Gallen
city: Thun
country: Switzerland
facility: Regionalspital
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Klinik Hirslanden
city: Zurich
country: Switzerland
facility: City Hospital Triemli
city: Zurich
country: Switzerland
facility: UniversitaetsSpital Zuerich
Study officials:
affiliation: Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
name: Emanuele Zucca, MD
role: STUDY_CHAIR
affiliation: Karolinska Institutet
name: Eva K. Kimby, MD, PhD
role: STUDY_CHAIR
affiliation: Cantonal Hospital of St. Gallen
name: Felicitas Hitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ullevaal University Hospital
name: Bjorn Ostenstad, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.