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

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rituximab
lenalidomide
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Haukeland Hospital - University of Bergen
  • Sorlandet Sykehus HF Kristiansand
  • Ullevaal University Hospital
  • Helse Stavanger HF
  • University Hospital of North Norway - Tromso
  • St. Olavs University Hospital
  • Sahlgrenska University Hospital
  • University Hospital of Linkoping
  • Sunderbyn Hospital
  • Lund University Hospital
  • Karolinska University Hospital - Huddinge
  • Karolinska University Hospital - Solna
  • Sundsvall Hospital
  • Norrlands University Hospital
  • Uppsala University Hospital
  • Kantonsspital Aarau
  • Kantonsspital Baden
  • Saint Claraspital AG
  • Universitaetsspital-Basel
  • Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
  • Inselspital Bern
  • Spitalzentrum Oberwallis - Brig
  • Kantonsspital Bruderholz
  • Kantonsspital Graubuenden
  • University Hospital
  • Kantonsspital Liestal
  • Kantonsspital Olten
  • Kantonsspital - St. Gallen
  • Regionalspital
  • Kantonsspital Winterthur
  • Klinik Hirslanden
  • City Hospital Triemli
  • UniversitaetsSpital Zuerich

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Rituximab

Rituximab plus Lenalidomide

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)
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)
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
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.
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.
Adverse events, including laboratory abnormality assessments and vital signs
This will be evaluated using the NCI CTCAE v4.0

Full Information

First Posted
March 1, 2011
Last Updated
June 26, 2023
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT01307605
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
It was decided by the trial team to stop the collection of follow up data in trial SAKK 35/10.
Study Start Date
February 9, 2011 (Actual)
Primary Completion Date
June 20, 2014 (Actual)
Study Completion Date
January 25, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
154 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Active Comparator
Arm Description
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
Arm Title
Rituximab plus Lenalidomide
Arm Type
Active Comparator
Arm Description
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
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituximab (MabThera)
Intervention Description
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
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
Lenalidomide (Revlimid)
Intervention Description
Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.
Primary Outcome Measure Information:
Title
Complete response (CR)
Description
The evaluation of CR is outlined in Appendix 1 Criteria for Evaluation of Response in Non-Hodgkin's Lymphoma.
Time Frame
at week 23
Secondary Outcome Measure Information:
Title
Best overall response (OR)
Description
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)
Time Frame
within 24 weeks
Title
Best Overall response (OR)
Description
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)
Time Frame
within 12 weeks
Title
Progression-free survival
Description
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 Frame
until disease progression, for up to 10 years after randomization
Title
Time to first off-trial anti-lymphoma therapy
Description
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.
Time Frame
until off-trial therapy administration, for up to 10 years after randomization
Title
Overall survival
Description
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.
Time Frame
every 6 months for up to 10 years after randomization
Title
Adverse events, including laboratory abnormality assessments and vital signs
Description
This will be evaluated using the NCI CTCAE v4.0
Time Frame
from inclusion until 30 days after treatment discontinuation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emanuele Zucca, MD
Organizational Affiliation
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eva K. Kimby, MD, PhD
Organizational Affiliation
Karolinska Institutet
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Felicitas Hitz, MD
Organizational Affiliation
Cantonal Hospital of St. Gallen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bjorn Ostenstad, MD
Organizational Affiliation
Ullevaal University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haukeland Hospital - University of Bergen
City
Bergen
ZIP/Postal Code
N-5021
Country
Norway
Facility Name
Sorlandet Sykehus HF Kristiansand
City
Kristiansand
ZIP/Postal Code
4604
Country
Norway
Facility Name
Ullevaal University Hospital
City
Oslo
ZIP/Postal Code
0424
Country
Norway
Facility Name
Helse Stavanger HF
City
Stavanger
ZIP/Postal Code
4068
Country
Norway
Facility Name
University Hospital of North Norway - Tromso
City
Tromso
ZIP/Postal Code
9038
Country
Norway
Facility Name
St. Olavs University Hospital
City
Trondheim
ZIP/Postal Code
7006
Country
Norway
Facility Name
Sahlgrenska University Hospital
City
Göteborg
ZIP/Postal Code
S-413 45
Country
Sweden
Facility Name
University Hospital of Linkoping
City
Linkoping
ZIP/Postal Code
S-581 85
Country
Sweden
Facility Name
Sunderbyn Hospital
City
Lulea
ZIP/Postal Code
95128
Country
Sweden
Facility Name
Lund University Hospital
City
Lund
ZIP/Postal Code
SE-22185
Country
Sweden
Facility Name
Karolinska University Hospital - Huddinge
City
Stockholm
ZIP/Postal Code
S-141 86
Country
Sweden
Facility Name
Karolinska University Hospital - Solna
City
Stockholm
ZIP/Postal Code
S-171 76
Country
Sweden
Facility Name
Sundsvall Hospital
City
Sundsvall
ZIP/Postal Code
85186
Country
Sweden
Facility Name
Norrlands University Hospital
City
Umea
ZIP/Postal Code
S-90185
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
SE-75185
Country
Sweden
Facility Name
Kantonsspital Aarau
City
Aarau
ZIP/Postal Code
5001
Country
Switzerland
Facility Name
Kantonsspital Baden
City
Baden
ZIP/Postal Code
5404
Country
Switzerland
Facility Name
Saint Claraspital AG
City
Basel
ZIP/Postal Code
4016
Country
Switzerland
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Spitalzentrum Oberwallis - Brig
City
Brig
ZIP/Postal Code
3900
Country
Switzerland
Facility Name
Kantonsspital Bruderholz
City
Bruderholz
ZIP/Postal Code
4101
Country
Switzerland
Facility Name
Kantonsspital Graubuenden
City
Chur
ZIP/Postal Code
7000
Country
Switzerland
Facility Name
University Hospital
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland
Facility Name
Kantonsspital Liestal
City
Liestal
ZIP/Postal Code
4410
Country
Switzerland
Facility Name
Kantonsspital Olten
City
Olten
ZIP/Postal Code
4600
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
9007
Country
Switzerland
Facility Name
Regionalspital
City
Thun
ZIP/Postal Code
3600
Country
Switzerland
Facility Name
Kantonsspital Winterthur
City
Winterthur
ZIP/Postal Code
8401
Country
Switzerland
Facility Name
Klinik Hirslanden
City
Zurich
ZIP/Postal Code
8032
Country
Switzerland
Facility Name
City Hospital Triemli
City
Zurich
ZIP/Postal Code
8063
Country
Switzerland
Facility Name
UniversitaetsSpital Zuerich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32012230
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.
Results Reference
derived
PubMed Identifier
31101627
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.
Results Reference
derived

Learn more about this trial

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

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