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A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive (DLBCL and MCL) B-cell Lymphoma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Follicular Lymphoma Patients (Phase IB), Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)

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Trial Information

A Phase Ib/II Study of OBINUTUZUMAB Combined to LENALIDOMIDE for the Treatment of Relapsed/Refractory Follicular and Aggressive (DLBCL and MCL) B-cell Lymphoma

This study is an open label, multicenter study with two phases:

The Phase IB part of the study is a dose escalation study of lenalidomide (Revlimid)
administered orally during on 3 weeks of every 28-day cycle, in combination with fixed doses
of obinutuzumab (GA101) in relapsed/refractory follicular lymphoma patients.

The Phase II part of the study is an efficacy study of the association of the recommended
dose of lenalidomide associated with GA101 in 2 separate populations of patients:
relapsed/refractory follicular lymphoma in one cohort and relapsed/refractory aggressive
lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in the second cohort.
First, all patients will receive a combination of obinutuzumab and lenalidomide for a total
of 6 cycles. Patients who achieve at least a partial response after 6 cycles will receive a
maintenance treatment with obinutuzumab for 2 years and Lenalidomide for 1 year as
tolerated, or until disease progression.

Inclusion Criteria:

- Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade
1, 2, or 3a) patients

- Phase II: Patients with either histologically documented CD20-positive Diffuse
large-cell lymphoma or Mantle cell lymphoma (cohort 1) or follicular lymphoma, WHO
grade 1, 2 or 3a (cohort 2)

- Phase IB and II:

- Relapsed/refractory NHL after ≥1 prior R-containing regimen with no curative option

- Aged 18 years or more

- ECOG performance status 0, 1 or 2

- At least one bi-dimensionally measurable nodal or tumor lesion defined by CT scan as:
greatest transverse diameter > 1.5 cm and a short axis ≥ 10mm

- Signed inform consent

- Life expectancy ≥ 3 months.

- All subjects must be able to understand and fulfill the lenalidomide Pregnancy
Prevention Plan requirements (see in appendix)

Exclusion Criteria:

- Previous treatment with obinutuzumab or lenalidomide

- Known CD20 negative status at relapse/progression. Biopsy at relapse/progression is
recommended but not mandatory

- Central nervous system or meningeal involvement by lymphoma

- Contraindication to any drug contained in the study treatment regimen

- Known HIV or HTLV-1 infection, positive serology to HB surface antigen [HBsAg] or
total HB core antibody [anti-HB-c]) and Hepatitis C (Hepatitis C virus [HCV]

- Any serious active disease or co-morbid medical condition (such as New York Heart
Association Class II or IV cardiac disease, severe arrhythmia, myocardial infarction
within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary
disease (including obstructive pulmonary disease and history of bronchospasm or other
according to investigator's decision)

- Any of the following laboratory abnormalities unless secondary to underlying

- Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).

- Platelet count < 100,000/mm3 (100 x 109/L) unless due to lymphoma for phase II

- Serum SGOT/AST or SGPT/ALT 3.0 x upper limit of normal (ULN) unless disease

- Serum total bilirubin > 2.0 mg/dL (34 μmol/L), except if disease related or in
case of Gilbert syndrome

- Calculated creatinine clearance (Cockcroft-Gault formula or MDRD) of < 50 mL
/min. For phase II part of the study, patients with calculated creatinine
clearance between 30 and 50ml/min can be included and lenalidomide dose will be
adjusted as follows (10mg once daily)

- Prior history of malignancies other than lymphoma unless the subject has been free of
the disease for ≥ 5 years

- Any serious medical condition, laboratory abnormality (other than mentioned above),
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.

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

- Patients taking corticosteroids during 4 weeks before inclusion, unless administered
at a dose equivalent to ≤ 10 mg/day prednisone (over these 4 weeks)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determination of the recommended dose of lenalidomide in combination with fixed doses of GA101

Outcome Description:

The determination of the recommended dose of lenalidomide in combination with fixed doses of GA101 will be performed by a dose escalation approach. Dose Limiting Toxicities (DLTs) observed during the administration of the first 2 cycles of the study will be listed for each escalation step.

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Franck MORSCHHAUSER, Professor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lymphoma Study Association


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

October 2012

Completion Date:

November 2019

Related Keywords:

  • Follicular Lymphoma Patients (Phase IB)
  • Follicular and Agressive (DLBCL&MCL) B-cell Lymphoma Patients (Phase II)
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse