Revlimid Dose 25 mg in Association With (R-CHOP) in the Treatment Follicular Lymphoma

A Phase Ib/II Study of Escalating Doses of Revlimid in Association With R-CHOP (R2-CHOP) in the Treatment of B-cell Lymphoma

The purpose of the study is to assess the efficacy of the association of Lenalidomide (Revlimid) and R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, vincristine and Prednisone) in a population of patients with follicular lymphoma as measured by the response rate at the end of treatment.

Inclusion Criteria:

• Patients with follicular lymphoma, (WHO) grade 1, 2 or 3a with at least one of the following signs requiring initiation of treatment:

  • Bulky disease according to the GELF criteria: nodal or extra-nodal mass >7cm in its greater diameter
  • B symptoms
  • Elevated serum (LDH) or beta 2-microglobulin
  • Involvement of at least 3 nodal sites (each >3cm)
  • Symptomatic spleen enlargement
  • Compressive syndrome
  • Pleural or peritoneal effusion

• Aged from 18 to 70 years

• WHO performance status 0, 1 or 2

• Signed inform consent

• Life expectancy of ≥ 90 days (3 months).

• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL not more than 3 days from the start of study drug and must either commit to continued abstinence from heterosexual intercourse (and confirmed on a monthly basis) or begin one effective method of birth control, at least four weeks before she starts taking lenalidomide, and maintain that method throughout the entire duration of study drug therapy (including dose interruptions), and for four weeks after the end of study treatment with lenalidomide, even if she has amenorrhea. FCBP must also agree to pregnancy testing at least every three weeks and must be counseled at a minimum of every three weeks about pregnancy precautions and risks of fetal exposure.

• Men must agree not to father a child and agree to use a condom throughout study drug therapy, during any dose interruption, and for one week after cessation of study drug therapy, if their partner is pregnant or of child bearing potential. Men must also agree not to donate semen during study drug therapy and for one week after end of study drug therapy. Men must be counseled at a minimum of every 4 weeks about pregnancy precautions and risks of fetal exposure.

• All subjects must abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.

• Agree not to share study drug with another person and to return all unused study drug to the investigator.

  • A female patient is considered to have childbearing potential unless she meets at least one of the following criteria 1) Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential); or 2) Premature ovarian failure confirmed by a specialist gynaecologist or 3) Previous bilateral salpingo-oophorectomy (BSO), or hysterectomy, or 4) XY genotype, turner syndrome, uterine agenesis.

Exclusion Criteria:

• Previous treatment with immunotherapy or chemotherapy:

  • Chlorambucil or Cyclophosphamide per os alone during less than 6 months, if stopped more than one year before inclusion
  • Rituximab alone during less than three months, if stopped more than one year before inclusion

• Previous radiotherapy except if localized to one lymph node area

• Other type of lymphomas: Burkitt, T cell, lymphocytic, CD 20 negative

• Central nervous system or meningeal involvement

• Contraindication to any drug contained in the chemotherapy regimen

• (HIV) disease, active hepatitis B or C

• Any serious active disease or co-morbid medical condition (according to investigator's decision)

• Any of the following laboratory abnormalities.

  • Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).
  • Platelet count < 100,000/mm3 (100 x 109/L).
  • Serum (SGOT/AST) or (SGPT/ALT) 5.0 x upper limit of normal (ULN).
  • Serum total bilirubin > 2.0 mg/dL (34 µmol/L), except in case of hemolytic anemia.

• Calculated creatinine clearance (Cockcroft-Gault formula) of < 50 mL /min

• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or lactating females.

• Prior ≥ Grade 3 allergic reaction/hypersensitivity to thalidomide.

• Prior ≥ Grade 3 rash or any desquamating (blistering) rash while taking thalidomide.

• Subjects with ≥ Grade 2 neuropathy.

• Prior use of lenalidomide.

• Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug therapy.