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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01307605
Recruitment Status : Active, not recruiting
First Posted : March 3, 2011
Last Update Posted : March 9, 2020
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Tracking Information
First Submitted Date  ICMJE March 1, 2011
First Posted Date  ICMJE March 3, 2011
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE February 9, 2011
Actual Primary Completion Date June 20, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2017)
Complete response (CR) [ Time Frame: at week 23 ]
The evaluation of CR is outlined in Appendix 1 Criteria for Evaluation of Response in Non-Hodgkin's Lymphoma.
Original Primary Outcome Measures  ICMJE
 (submitted: March 2, 2011)
Complete response at week 23
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2017)
  • Best overall response (OR) [ Time Frame: within 24 weeks ]
    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)
  • Best Overall response (OR) [ Time Frame: within 12 weeks ]
    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)
  • Progression-free survival [ Time Frame: until disease progression, for up to 10 years after randomization ]
    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
  • Time to first off-trial anti-lymphoma therapy [ Time Frame: until off-trial therapy administration, for up to 10 years after randomization ]
    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.
  • Overall survival [ Time Frame: every 6 months for up to 10 years after randomization ]
    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.
  • Adverse events, including laboratory abnormality assessments and vital signs [ Time Frame: from inclusion until 30 days after treatment discontinuation ]
    This will be evaluated using the NCI CTCAE v4.0
Original Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2011)
  • Best overall response (OR) within 24 weeks
  • Best OR within 12 weeks
  • Best OR
  • Progression-free survival
  • Duration of complete response
  • Time to first off-trial anti-lymphoma therapy
  • Overall survival
  • Adverse events, including laboratory abnormality assessments and vital signs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab With or Without Lenalidomide in Treating Patients With Previously Untreated Follicular Lymphoma
Official Title  ICMJE Rituximab Plus Lenalidomide or Rituximab Monotherapy for Untreated Patients With Follicular Lymphoma in Need of Therapy. A Randomized, Open-Label, Multicenter Phase II Trial.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • 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
    Other Name: Rituximab (MabThera)
  • 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.
    Other Name: Lenalidomide (Revlimid)
Study Arms  ICMJE
  • Active Comparator: 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: Biological: Rituximab
  • Active Comparator: 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.
    Intervention: Drug: lenalidomide
Publications * Zucca E, Rondeau S, Vanazzi A, Østenstad 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 2, 2011)
152
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2023
Actual Primary Completion Date June 20, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway,   Sweden,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01307605
Other Study ID Numbers  ICMJE SAKK 35/10
SWS-SAKK-35-10
2010-021253-39 ( EudraCT Number )
CELGENE-SWS-SAKK-35/10 ( Other Grant/Funding Number: Celgene )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Swiss Group for Clinical Cancer Research
Study Sponsor  ICMJE Swiss Group for Clinical Cancer Research
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Emanuele Zucca, MD Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Study Chair: Eva K. Kimby, MD, PhD Karolinska Institutet
Principal Investigator: Felicitas Hitz, MD Cantonal Hospital of St. Gallen
Principal Investigator: Bjorn Ostenstad, MD Ullevaal University Hospital
PRS Account Swiss Group for Clinical Cancer Research
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP