E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Phase IB: CD20 positive Follicular Lymphoma, WHO grade 1, 2 or 3a relapsed/refractory after ≥1 prior R-containing regimen
Phase II: CD20 positive follicular and agressive B-cell lymphoma (Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma) relapsed/refractory after ≥1 prior R-containing regimen |
Phase IB: lymphome folliculaire CD20 positif grade 1 à 3a réfractaire ou en rechute après ≥1 ligne de chimiothérapie contenant du rituximab
Phase II: lymphome folliculaire CD20 positif et lymphome à cellules B agressif (Lymphome B diffus à grandes cellules et lymphome du manteau)réfractaire ou en rechute après ≥1 ligne de chimiothérapie contenant du rituximab |
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E.1.1.1 | Medical condition in easily understood language |
Phase I: follicular lymphoma relapsed after ≥1 regimen
Phase II: follicular lymhoma or agressive lymhoma relapsed after ≥1 regimen |
Phase IB: lymphome folliculaire en rechute après ≥1 chimiothérapie
Phase II: lymphome folliculaire et lymphome à cellules B agressif en rechute après ≥1 chimiothérapie |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016906 |
E.1.2 | Term | Follicle centre lymphoma, follicular grade I, II, III refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012822 |
E.1.2 | Term | Diffuse large B-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10026801 |
E.1.2 | Term | Mantle cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase IB: to determine the recommended dose (RD) of lenalinomide (Revlimid) when administered in association with obinutuzumab by escalation approach (3+3 dosing).
Phase II: to assess the efficacy of the association of the recommended dose of lenalidomide in combination with obinutuzumab, as measured by the overall response rate (ORR) at the end of 6 cycles in 2 different populations of patients with relapsed/refractory disease: follicular lymphoma and aggressive lymphoma [aNHL] (Diffuse large B-cell and Mantle cell lymphoma). |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of the combination of lenalidomide plus obinutuzumab during induction and maintenance therapy by monitoring all adverse and serious adverse events AEs/SAEs according to the NCICTCAE v. 4.
- To assess the efficacy of the combination of lenalidomide plus obinutuzumab: Complete response (CR) rate after 3 and 6 cycles, for
patients who received maintenance treatment OR and CR rate at the end of maintenance treatment, best overall response rate (BOR), event free survival (EFS), progression free survival (PFS), response duration (RD) and overall survival (OS). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A optionnal biological study is planned for 60 patients included in the study. This biological program includes phenotypic, plasmatic and functional analysis. |
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E.3 | Principal inclusion criteria |
Phase IB only: Histologically documented CD20-positive follicular lymphoma (WHO grade 1, 2, or 3a) patients
Phase II only: 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 of ≥ 3 months
- All subjects must be able to understand and fulfill the lenalidomide Pregnancy Prevention Plan requirements |
|
E.4 | Principal 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] antibody)
- Any serious active disease or co-morbid medical condition (such as New York Heart Association Class III 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.
o Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1.5 x 109/L).
o Platelet count < 100,000/mm3 (100 x 109/L) unless due to lymphoma for phase II part.
o Serum SGOT/AST or SGPT/ALT 3.0 x upper limit of normal (ULN) unless disease involvement.
o 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase IB: the determination of the recommended dose (RD) of lenalidomide in combination with fixed doses of GA101 by a dose escalation approach (3+3design).
Phase II: the efficacy of the recommended dose of lenalidomide in combination with GA101 will be measured by the overall response rate ORR by IWG criteria (Cheson 1999) at the end of 6 cycles in 2 different populations of patients with relapsed/refractory disease: follicular lymphoma and aggressive lymphoma [aNHL] (Diffuse large B-cell and Mantle cell lymphoma) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I: at the end of cycle 1 (after 28 days)
Phase II: at the end of cycle 6 (after 6 months) |
|
E.5.2 | Secondary end point(s) |
- Safety of study treatment will be evaluated during induction and maintenance by monitoring all adverse and serious adverse events AEs/SAEs according to the NCI-CTCAE v. 4.
- Efficacy will be evaluated by CR rate after 3 and 6 cycles, OR and CR rate at the end of maintenance treatment, BOR, EFS, PFS, RD and OS. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- All adverse events will be reported during the study period up to 28 days after the last drug administration regardless the relationship with study drug and after this period if the event is related to the study drug
- after 3 and 6 cycles (after 3 and 6 months) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Determination of the recommended dose of lenalidomide in combination with GA101 |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |