Clinical trial NCT00901615: Lenalidomide and R-CHOP in B-cell Lymphoma
Official title: A Phase IB Study of Escalating Doses of REVLIMID in Association With R-CHOP (R2-CHOP) in the Treatment of B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse
Follicular Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Keywords: lymphoma
lenalidomide
gela
Lead sponsor: Lymphoma Study Association
Sponsor class: OTHER
First posted: 2009-05-14
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine the recommended dose (RD) of lenalidomide (Revlimid) when administered in association with R-CHOP (rituximab (R), cyclophosphamide, doxorubicin, vincristine and prednisone).

Detailed description: The study is a dose escalation study of lenalidomide (Revlimid) administered orally during 14 days in combination with fixed doses of rituximab (R), cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered every 3 weeks (R-CHOP 21) in patients with B-cell lymphoma.

Eligibility criteria: Inclusion Criteria:

* Patients with one of the following B-cell Lymphoma, CD 20 positive:

  * Mantle cell, Marginal zone, follicular
  * Histological transformation from low grade to high grade
  * Diffuse large B cell
* 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 or begin one acceptable method of birth control, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to monthly pregnancy testing and must be counseled at a minimum of every 4 weeks about pregnancy precautions and risks of fetal exposure.
* Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. Men must also be counseled at a minimum of every 4 weeks about pregnancy precautions and risks of fetal exposure.

  * † 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, or hysterectomy, or 4) XY genotype, turner syndrome, uterine agenesis.

Exclusion Criteria:

* Previous treatment with immunotherapy or chemotherapy except:

  * 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities
timeFrame: 42 days
Secondary outcomes:
measure: Complete response rate and Overall response rate at the end of treatment
timeFrame: 3 months after the end of treatment
measure: Complete and Overall response rates after induction
timeFrame: at the end of third cycle of treatment (between Day 56 and Day 63)
measure: Progression-Free Survival and Overall survival
timeFrame: 7 years
measure: Duration of response
timeFrame: 7 years
measure: Collection of adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: CHRU Lille
city: Pierre Benite
country: France
facility: CHU Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: Lymphoma Study Association
name: Hervé TILLY, Prof
role: PRINCIPAL_INVESTIGATOR
References: