E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed malignant B-cell lymphoma
- CD 20 positive disease
- Entities:
- Diffuse large B-cell Lymphoma
- Follicular lymphoma grade IIIB
- Transformed indolent lymphoma up to 20% of the patient population
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E.1.1.1 | Medical condition in easily understood language |
Relapsed malignant B-cell lymphoma
- Entities:
- Diffuse large B-cell Lymphoma
- Follicular lymphoma
- Transformed indolent lymphoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 evaluate the overall response rate (ORR) of the combination after completion or termination of trial treatment |
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E.2.2 | Secondary objectives of the trial |
- To evaluate safety/toxicity
- To evaluate remission duration and survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients aged ≥ 18 years
- Histologically proven diagnosis of diffuse large cell B-cell lymphoma, follicular lymphoma IIIB or transformed
indolent lymphoma according to the World Health Organization classification (central pathology review)
- Relapsed disease
- Eastern Cooperative Oncology Group [ECOG] performance Status ≤2, unless tumor associated
- Adequate cardiac reserve: Serum Troponin level must be consistent with no significant acute or chronic myocardial damage and there should be no evidence of symptomatic disease
- No curative option available
- At least 1 measurable tumor mass (>1.5 cm x >1.0 cm) or bone marrow infiltration
- Adequate bone marrow reserve: Platelets of at least 100.000/µl, absolute neutrophil count of at least 1000/µl.
Adequate hepatic and renal function: Alanine aminotransferase <2.5 x upper limit of normal (ULN); Aspartate
aminotransferase <2.5 x ULN, total bilirubin <1.5 x ULN
- No active Hepatitis B or C or HIV-infection
- Measured or calculated creatinine clearance >30 mL/min
- Fresh tumor biopsy or archived tissue available
- Ability of patients to understand nature, importance and individual consequences of clinical trial.
- Signed informed consent
- Women post-menopausal for more than two years can participate in the trial. Women with childbearing
potential can only participate, if they are surgically sterile or a negative pregnancy test (serum or urine) is
available before trial and they are willing to practice a highly effective and medically accepted contraception
method during trial and for a period of 18 months post-treatment. Reliable contraception comprises systematic
contraceptives (oral, implant, injection) or diaphragm / condoms / intrauterine devices (IUP) with spermicide.
- Male patients are advised to use contraceptive methods (preferably barrier) during treatment and for a period
of 6 months post-treatment
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E.4 | Principal exclusion criteria |
- Lymphoma other than DLBCL, FL IIIB, transformed indolent NHL
- CNS involvement (brain MRI is required only in cases of clinically suspicious involvement)
- Pregnant or breast-feeding women
- Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled
diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinaemia)
- Myocardial infarction within the last 6 months
- Active uncontrolled infections including HIV-positivity, active Hepatitis B or C
- Vaccination with live vaccine within last 4 weeks
- Mental status precluding patient’s compliance
- Known CD20 negativity
- Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer,
curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with
no evidence of disease for >3 years, or prostate cancer with a life expectancy of more than 2 years
- Treatment with any approved anticancer agent within last 2 weeks. Any agents must have been stopped at
least 2 weeks prior to day 1 of GOAL treatment and all treatment related adverse events must have returned
to Grade 1.
- Prior exposition to Obinutuzumab or Pixantrone
- History of hypersensitivity to medicinal products with similar chemical structure as the trial medication
- Active participation in other interventional clinical trials during the present clinical trial or within the last 2
weeks prior to treatment initiation. Concurrent participation in non-treatment studies is not excluded
- Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the ORR of the regimen at cycle 6 or the individual treatment end. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Active treatment with Obinutuzumab and Pixantrone for 6 cycles will last approximately to a maximum of 24 weeks. Response will be assessed 4 weeks after completion of treatment. In patients with early termination the appropriate response evaluation will be used. |
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E.5.2 | Secondary end point(s) |
- Rate of adverse events / Tolerability
- Progression free survival
- Overall survival
- ORR in separate GCB vs. non GCB-analysis is planned (GEP-profiling)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Active treatment with Obinutuzumab and Pixantrone for 6 cycles will last approximately to a maximum of 24 weeks. Response will be assessed 4 weeks after completion of treatment. Patients will be followed for disease progression and or death and initiation of subsequent therapy for B-cell lymphoma for at least 2 years (if no event occurs) up to a maximum of 3 years. |
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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 | 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) | 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) | 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 | No |
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 | No |
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 | 12 |
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 | 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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End of trial as defined as last patient last treatment plus a maximum of 3 years follow-up or latest patient alive followed for 3 years. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |