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

Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01307605
• Other study ID #: SAKK 35/10
• Secondary ID: SWS-SAKK-35-1020
• Status: Terminated
• Phase: Phase 2
• Start date: February 9, 2011
• Est. completion date: January 25, 2023

Study information

• Verified date: June 2023
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 154
• Est. completion date: January 25, 2023
• Est. primary completion date: June 20, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• 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

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

Locations

Country	Name	City	State
Norway	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	Tromso
Norway	St. Olavs University Hospital	Trondheim
Sweden	Sahlgrenska University Hospital	Göteborg
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Sunderbyn Hospital	Lulea
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	Umea
Sweden	Uppsala University Hospital	Uppsala
Switzerland	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	St. Gallen
Switzerland	Regionalspital	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	City Hospital Triemli	Zurich
Switzerland	Klinik Hirslanden	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Countries where clinical trial is conducted

Norway,  Sweden,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Best overall response (OR)	OR is defined as either: the disappearance of all evidence of disease (CR or CRu); the regression of measurable disease with no new sites (PR)	within 24 weeks
Secondary	Best Overall response (OR)	OR is defined as either: the disappearance of all evidence of disease (CR or CRu); the regression of measurable disease with no new sites (PR)	within 12 weeks
Secondary	Progression-free survival	PFS will be calculated from randomization until the first event of interest: disease progression or relapse according to criteria of Cheson et a.l 1999; death from any cause	until disease progression, for up to 10 years after randomization
Secondary	Time to first off-trial anti-lymphoma therapy	This will be calculated from randomization until the start of the first off-trial anti-lymphoma treatment.; Patients not receiving any off-trial anti-lymphoma treatment will be censored at the last follow-up visit.	until off-trial therapy administration, for up to 10 years after randomization
Secondary	Overall survival	OS will be calculated from randomization until death. Patients not experiencing an event will be censored at the last date they were known to be alive.	every 6 months for up to 10 years after randomization
Secondary	Adverse events, including laboratory abnormality assessments and vital signs	This will be evaluated using the NCI CTCAE v4.0	from inclusion until 30 days after treatment discontinuation