E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma is a type of cancer of the white blood cells (these cells are part of the body's immune system) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016904 |
E.1.2 | Term | Follicle centre lymphoma, follicular grade I, II, III NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 |
• To determine the recommended Phase II dose (RP2D) for lenalidomide (Len) when given in combination with fixed doses of obinutuzumab (G) and atezolizumab (Atezo)
• To evaluate the safety and tolerability of Atezo +G+ Len
• To evaluate the efficacy of induction treatment with Atezo+G+ Len on the basis of the following endpoint:
o complete response (CR) at end of induction (EOI) as determined by the Independent Review Committee (IRC) on the basis of positron emission tomography - computed tomography (PET-CT) scans
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of induction and maintenance treatments with Atezo +G+ Len
• To characterize the pharmacokinetics of atezolizumab, obinutuzumab, and lenalidomide, when given in combination
• To evaluate the immune response to obinutuzumab and to atezolizumab
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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 |
Specimens for the Roche Clinical Repository (RCR) will be collected from patients who give specific consent to participate in this optional research with the following objectives:
• To study the association of biomarkers with efficacy, adverse events, or disease progression
• To increase knowledge and understanding of disease biology
• To study drug response, including drug effects and the processes of drug absorption and disposition
• To develop biomarker or diagnostic assays and establish the performance characteristucs of these assays
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E.3 | Principal inclusion criteria |
• Age >=18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Relapsed or refractory FL after treatment with at least one prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists as determined by the investigator
• Histologically documented CD20-positive lymphoma as determined by the local laboratory
• Fluorodeoxyglucose-avid lymphoma (i.e., PET-positive lymphoma)
• At least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or magnetic resonance imaging [MRI])
• Availability of a representative tumor specimen and the corresponding pathology report for retrospective central confirmation of the diagnosis of FL
• Agreement to comply with all local requirements of the lenalidomide risk minimization plan
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), and for at least 18 months after the last dose of study treatment
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm for at least 3 months after the last dose of study treatment. |
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E.4 | Principal exclusion criteria |
• Grade 3b follicular lymphoma
• History of transformation of indolent disease to DLBCL
• Known history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia or evidence of active pneumonitis at screening.
• Known CD20-negative status at relapse or progression
• Central nervous system lymphoma or leptomeningeal infiltration
• Prior allogeneic stem-cell transplantation (SCT)
• Completion of autologous SCT within 100 days prior to Day (D) 1 of Cycle (C) 1
• Prior standard or investigational anti-cancer therapy as specified in protocol
• History of resistance to lenalidomide or response duration of <1 year
• Treatment with systemic immunosuppressive medications
• History of solid organ transplantation
• Clinically significant toxicity from prior therapy that has not resolved to Grade ≤ 2 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], v4.0) prior to Day 1 of Cycle 1
• History of erythema multiforme, Grade ≥ 3 rash, or blistering following prior treatment with immunomodulatory derivatives such as thalidomide and lenalidomide
• Active bacterial, viral, fungal, or other infection or IV antibiotics within 4 weeks of Day 1 of Cycle 1
• Positive for hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody at screening
• Known history of HIV positive status
• History of progressive multifocal leukoencephalopathy
• History of autoimmune disease
• Contraindication to treatment for thromboembolism prophylaxis
• Grade ≥ 2 neuropathy
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Evidence of any significant, uncontrolled concomitant disease
• Inadequate hematologic function (unless due to underlying lymphoma)
• Abnormal laboratory values (unless due to underlying lymphoma)
• Pregnant or lactating or intending to become pregnant during the study
• History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies
• Vaccination with a live virus vaccine within 28 days prior to Day 1 of Cycle 1 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety:
1. Incidence of DLTs during cycle 2 of study treatment
2. Incidence of adverse events
3. Changes in vital signs, ECG and clinical laboratory results
Efficacy:
4. CR at EOI as determined by the IRC on the basis of PET-CT scans
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety:
1. Day 1-Day 28 of second cycle
2. Up to 35 days after the last dose of study treatment
3. Up to 35 days after the last dose of study treatment
Efficacy:
4. 6-8 weeks after Day 1 of the last induction cycle
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E.5.2 | Secondary end point(s) |
Efficacy:
1. CR at EOI, as determined by the investigator on the basis of PET-CT scans
2. CR at EOI, as determined by the IRC and by the investigator on the basis of CT scans alone
3. Objective response (defined as a CR or partial response [PR]) at EOI, as determined by the IRC and by the investigator on the basis of PET-CT scans
4. Objective response (defined as a CR or PR) at EOI, as determined by the IRC and by the investigator on the basis of CT scans alone
5. Best response of CR or PR during the study, as determined by the investigator on the basis of CT scans alone
PK:
6. Observed serum obinutuzumab concentration at specified timepoints
7. Observed serum atezolizumab concentration at specified timepoints
8. Observed plasma lenalidomide concentration at specified timepoints
Immunogenicity:
9. Incidence of human anti-human antibodies (HAHAs) to obinutuzumab during the study relative to the prevalence of HAHAs at baseline
10. Incidence of anti-therapeutic antibodies to atezolizumab during the study relative to the prevalence of anti-therapeutic antibodies at baseline |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy:
1 - 4. 6-8 weeks after Day 1 of the last induction cycle
5. Every 6 months after the induction treatment, until disease progression, initiation of another anti-lymphoma treatment or end of study, whichever occurs first
PK:
6. Cycle (C) 1 Day (D) 1, C2D1, C4D1, and C6D1, Month (M) 1 D1, M7, 13 and 19 D1, at treatment discontinuation (TD), 120 days and 1 year after the last dose of obinutuzumab
7. C2D1 and 15, C4D1, and C6D1, M1D1 and 2, M4, 7, 13 and 19 D1, at TD, 120 days and 1 year after the last dose of atezolizumab
8. C1D1 and 15, C2D15, C6D15
Immunogenicity:
9. C1D1, C6D1, at TD, 120 days and 1 year after the last dose of obinutuzumab
10. C2D1 and 15, C4D1, and C6D1, M1D1, M4, 7, 13 and 19 D1, at TD, 120 days and 1 year after the last dose of atezolizumab |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 |
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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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Dose escalation and expansion |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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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The end of this study is defined as the time when all enrolled patients have completed or discontinued study treatment (including induction treatment and maintenance treatment as applicable). |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |