E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated stage III or IV non-Hodgkin’s lymphoma (CD20+ Follicular Lymphoma of Grade 1, 2 or 3a, requiring chemotherapy) |
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E.1.1.1 | Medical condition in easily understood language |
Follicular Non-Hodgkin’s lymphoma not previously treated |
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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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10016903 |
E.1.2 | Term | Follicle centre lymphomas, follicular grade I, II, III |
E.1.2 | System Organ Class | 100000004851 |
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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 |
The primary objective of this trial is to compare the efficacy (best overall response rate after completion of induction therapy) of BI 695500 plus chemotherapy versus rituximab plus chemotherapy in patients with untreated follicular lymphoma |
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E.2.2 | Secondary objectives of the trial |
1/ To assess Progression Free Survival (PFS), Time to Treatment Failure (TTF) and Overal Survival (OS)
2/ To evaluate safety and immunogenicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female patients, at least 18 years of age at Screening.
- Untreated, histologically confirmed, stage III or IV NHL (CD20+ Follicular Lymphoma of Grade 1, 2 or 3a, requiring chemotherapy).
- Patients not previously treated. Eligible patients previously on watch and wait (i.e., those patients who do not require treatment upfront at the time of the diagnosis) can enter the trial.
- ECOG performance status of 0 to 2.
- Have at least one measurable lesion as per the IWG criteria 2007 at Screening.
- Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to randomization, including:
• Hemoglobin ≥ 9.0 g/dL (≥ 5.6 mmol/L).
• Absolute neutrophil count ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L.
- Adequate renal and liver function
- For participants of reproductive potential (males and females), use of a medically acceptable method of contraception during the trial. |
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E.4 | Principal exclusion criteria |
- Transformation to high-grade lymphoma (secondary to low grade lymphoma).
- Presence or history of central nervous system (CNS) lymphoma.
- Patients receiving current treatment with oral corticosteroids must not be receiving a dose exceeding 20 mg/day prednisone or equivalent.
- Previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, idarubicin and/or other anthracyclines and anthracenediones.
- Patients with prior or concomitant malignancies.
- Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.
- Poor renal function: serum creatinine > 2.0 mg/dL (> 197 mcmol/L).
- Poor hepatic function: total bilirubin > 2.0 mg/dL (> 34 mcmol/L) or aspartate aminotransferase (AST) > 3 times the upper limit of normal.
- Active, chronic or persistent infection that might worsen with immunosuppressive treatment.
- Patients known to be seropositive for HBV or have active HBV infection.
- Serious underlying medical conditions, which per the investigator's discretion could impair the ability of the patient to participate in the trial.
- Patients with uncontrolled hypertension.
- Known sensitivity or allergy to murine products.
- History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the trial drug.
- Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.
- Treatment within a clinical trial within 4 weeks prior initiation of trial treatment.
- Refusal from patients with reproductive potential (males and females), of use of a medically acceptable method of contraception during the trial, i.e., a combination of two forms of effective contraception.
- Pregnancy or breast feeding
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of the trial is the best overall response rate (CR+PR) after completion of induction therapy, as defined by the modified IWG Criteria, 2007, using the investigator’s assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessment and Response assessment are performed after 3 cycles of induction treatment, at the end of induction therapy and every 6 months during maintenance therapy. The primary analysis (best overall response rate [CR+PR]), will be performed after all patients have had tumor response assessments performed on completion of induction therapy or earlier if no more patients are expected to complete induction therapy. |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are Progression Free Survival, Time to Treatment Failure, Overall Survival and immunogenicity.
An additional secondary endpoint is to evaluate safety of BI 695500 by means of Adverse Events, laboratory tests, physical examination, vital signs and 12¬lead electrocardiogram (ECG). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor assessment and Response assessment are performed after 3 cycles of induction treatment, at the end of induction therapy and every 6 months during maintenance therapy. Suvival will be assessed throughout the trial from C1 to End of Maintenance visit. Anti-drug antibodies will be assessed at C1, C4, C6,End of Induction, every 8 weeks during maintenance, at End of Maintenance visit.
Timepoints for safety endpoint: Safety enpoints are checked at each study visit. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 118 |
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 |
Argentina |
Australia |
Belgium |
Bosnia and Herzegovina |
Brazil |
Bulgaria |
Chile |
Croatia |
Czech Republic |
Denmark |
Egypt |
France |
Germany |
Guatemala |
Hong Kong |
Hungary |
India |
Indonesia |
Italy |
Korea, Republic of |
Malaysia |
Mexico |
Netherlands |
New Zealand |
Panama |
Peru |
Philippines |
Poland |
Romania |
Russian Federation |
Saudi Arabia |
Serbia |
Singapore |
Slovakia |
South Africa |
Spain |
Sri Lanka |
Taiwan |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
Vietnam |
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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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Final analysis will be conducted when the last patient completes maintenance therapy or earlier. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |