A Phase 3 open-label randomized study tocompare the efficacy and safety of rituximabplus lenalidomide versus rituximab pluschemotherapy followed by rituximab in subjectswith previously untreated follicular lymphoma (ALLG NHL27)
- Conditions
- follicular lymphomaCancer - Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
- Registration Number
- ACTRN12612001045808
- Lead Sponsor
- The Lymphoma academic research organisation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 775
1. Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a as assessed by the investigators:
2. Have no prior systemic treatment for lymphoma.
3. Must be in need of treatment as evidenced by at least one of the following criteria:
Bulky disease defined as:
-a nodal or extranodal (except spleen) mass > 7cm in its
greater diameter or,
-involvement of at least 3 nodal or extranodal sites (each
with a diameter greater than >3 cm)
Presence of at least one of the following B symptoms:
-fever (>38 degrees Celcius) of unclear etiology
-night sweats
-weight loss greater than 10% within the prior 6 months
Symptomatic splenomegaly
Compression syndrome (ureteral, orbital, gastrointestinal)
Any one of the following cytopenias due to lymphoma:
-hemoglobin < 10g/dL (6.25 mmol/L)
-platelets <100 x 10^9/L , or
-absolute neutrophil count (ANC) < 1.5 x 10^9/L
Pleural or peritoneal serous effusion (irrespective of cell
content)
LDH> upper limit of normal (ULN) or beta 2 microglobulin > ULN
4. Bi-dimensionally measurable disease with at least one mass lesion > 2cm that was not previously irradiated.
5. Stage II, III or IV disease.
6. Must be > or = to 18 years and sign an informed consent.
7. Performance status less than or equal to 2 on the ECOG scale.
8. Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to signing informed consent, including:
-Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
-Platelet count greater than or equal to 75 x 10^9/L
-Hemoglobin greater than or equal to 8.0 g/dl (5 mmol/L)
9. Must be able to adhere to the study visit schedule and other protocol requirements.
10. Females of childbearing potential (FCBP) receiving lenalidomide must:
-Have two negative pregnancy tests as verified by the study
doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
-Either commit to complete abstinence from heterosexual
contact(which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
11. Male patients receiving lenalidomide must:
Must practice complete abstinence or agree to use a condom
during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study, during
dose interruptions and for at least 28 days following study
drug discontinuation, even if he has undergone a successful
vasectomy.
Agree to not donate semen during study drug therapy and for 28 days after discontinuation of study drug therapy.
12. All patients receiving lenalidomide must:
Have an understanding that the study drug could have a potential teratogenic risk.
Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of study drug therapy.
Agree not to share study medication with another person.
Agree to be counseled about pregnancy precautions and risk of fetal exposure
Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug
discontinuation.
13. For all patien
1. Clinical evidence of transformed lymphoma by investigator assessment.
2. Grade 3b follicular lymphoma.
3. Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisolone (over these 4 weeks).
4. Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent.
5. Seropositive for or active viral infection with hepatitis B virus (HBV):
-HBsAg positive
-HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA
Note:
-Patients who are HBsAg negative, anti-HBs positive and/or anti HBc positive but viral DNA negative are eligible
-Patients who are seropositive due to a history of hepatitis B vaccine are eligible.
6. Known seropositive for, or active infection hepatitis C virus (HCV).
7. Known seropositive for, or active viral infection with human immunodeficiency virus (HIV).
8. Life expectancy < 6 months.
9. Known sensitivity or allergy to murine products.
10. Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for greater than or equal to 10 years. Exceptions include a history of previously treated:
a. Localized non-melanoma skin cancer
b. Carcinoma in situ of the cervix
11. Prior use of lenalidomide.
12. Neuropathy > Grade 1.
13. Presence or history of CNS involvement by lymphoma.
14. Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis.
15. Any of the following laboratory abnormalities:
-serum aspartate transaminase (AST/SGOT) or alanine
transaminase (ALT/SGPT) > 3x upper limit of normal (ULN),
except in patients with documented liver or pancreatic
involvement by lymphoma
-total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma
-creatinine clearance of < 30 mL/min
16. Uncontrolled intercurrent illness.
17. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
18. Pregnant or lactating females.
19. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary objective of the study is to compare the efficacy of rituximab plus lenalidomide to rituximab plus chemotherapy followed by rituximab in patients with previously untreated follicular lymphoma. Efficacy determination will be based upon the co-primary endpoints of complete response (CR/CRu) rate at 120 weeks and progression free survival (PFS) assessed by the international review committee (IRC) using the independent working group (IWG) (Cheson, 1999) criteria.[120 weeks for CR; for PFS from randomization into the study to the first observation of documented disease<br>progression or death due to any cause, or censored at the last patient visit]
- Secondary Outcome Measures
Name Time Method Time to Treatment Failure (TTF)[TTF will be measured from the date of randomization to the date of first documented treatment<br>discontinuation for any reason, including disease progression, treatment toxicity, and deaths.];Event Free Survival (EFS)[EFS will be measured from the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.];Time to Next Anti-Lymphoma Treatment (TTNLT)[TTNLT will be measured from the date of randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radioimmunotherapy, immunotherapy) or censored at the last patient visit];Overall Survival (OS)[End of trial; approximately when the first accrued patient has received 10 years follow up.]