A randomised phase I/II trial of lenalidomide and rituximab with or withoutbendamustine in patients = 18 years with relapsed follicular lymphoma

• Conditions: Follicular lymphoma.; MedDRA version: 18.0Level: PTClassification code 10003903Term: B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: PTClassification code 10003902Term: B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000097-56-GB
• Lead Sponsor: HOVON Foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-21
• Last Update Posted: 28 September 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

? Relapsed FL grade 1, 2, 3a;
? Ann Arbor stage II-IV at relapse;
? A biopsy or FNA to show CD20 postivity is required. A biopsy/FNA performed at any time since the most recent therapy is acceptable as long as this shows FL and there is no clinical concern for transformation at the time of study entry. In case clinically transformation is suspected, a biopsy should be obtained at the time of study entry to exclude transformation;
? A maximum of three prior systemic treatment regimens (patients who have had a prior allogeneic SCT are excluded; prior autologous SCT (if > 1 year ago) is allowed);
? Prior bendamustine is allowed, under the following conditions:
? 1)Only one prior treatment (with a maximum of 6 cycles) with bendamustine is
allowed
? 2)Patients must have had a PR or CR following prior use of bendamustine
? 3)Prior treatment with bendamustine must have taken place =24 months ago
(measured from the start of prior bendamustine treatment, i.e. approximately 18
months from the end of prior bendamustine treatment)

? Subjects must have an indication for treatment based on one or more of the following criteria:
- Involvement of at least 3 nodal sites, each with a diameter > 3 cm
- Symptomatic splenomegaly
- Bulky disease at study entry according to the GELF criteria: nodal or extranodal mass (except spleen) > 7 cm in its greatest diameter
- B-symptoms (absence or presence of fever and/or night sweats and/or unexplained loss of 10% of body weight or more in the 6 months preceding diagnosis)
- Hb < 10 g/dl (6.2 mmol/l) (if caused by bone marrow infiltration and not otherwise
explained)
- Thrombocytopenia: platelets < 100x109/l caused by bone marrow infiltration
- Organ compression syndrome (e.g. hydronephrosis caused by lymphadenopathy)
- Pleural/peritoneal effusion
- Symptomatic extranodal manifestations;

? Measurable disease (patients with only bone marrow involvement are therefore not eligible);
? Age = 18 years;
? Able to adhere to the study visit schedule and other protocol requirements;
? WHO performance status of 0-2;
? Laboratory test results within these ranges: absolute neutrophil count = 1.5x 109/l, platelet count = 100x 109/l (unless bone marrow infiltration), creatinine clearance = 50 ml/min, total bilirubin = 30 µmol/l (1,75 mg/dl), AST & ALT = 3x ULN;
? Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting lenalidomide treatment;
? Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all pre-menopausal women). Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention
? Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

? Rituximab-refractory patients (definition: progression during or within 6 months after rituximab containing immunochemotherapy or rituximab maintenance treatment);
? Clinical or histologic signs of transformation or prior transformed phase of FL;
? Prior allogeneic SCT;
? Prior autologous SCT less than one year ago;
? Any prior use of lenalidomide;
? Concurrent use of other anti-cancer agents or treatments;
? Concurrent use of allopurinol, e.g. because of gout. Patients with gout are advised to switch to another anti-gout medication, because of the risk of Stevens-Johnson Syndrome observed in patients using bendamustine and allopurinol;
? Use of any other experimental drug or therapy within 28 days of baseline;
? Hepatitis B (including HBcAb) positive, Hepatitis C positive and/or HIV positive patients;
? Patients with uncontrolled autoimmune hemolytic anemia (AIHA) or autoimmune
thrombocytopenia (ITP);
? Active fungal, bacterial, and/or viral infection;
? Recent vaccination for yellow fever (within 4 weeks before registration)
? Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide);
? Known hypersensitivity and/or serious adverse reactions to lenalidomide or similar drugs;
? Intolerance of exogenous protein administration, or known allergy to murine products;
? Uncontrolled hyperthyroidism or hypothyroidism;
? Neuropathy = grade 2 at time of inclusion;
? Clinically symptomatic severe cardiac dysfunction (NYHA III-IV);
? Clinically symptomatic severe pulmonary dysfunction;
? Severe neurologic or psychiatric diseases;
? Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,
infection);
? History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer (TNM stage of T1a or T1b);
? Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified