E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study evaluate anti-tumor efficacy and safety of GM-CSF (sargramostim, Leukine®) associated with Rituximab (MabThera®) and chemotherapy (CHOP) in patients with non bulky follicular non Hodgkin’s lymphoma with no prior treatment. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025310 |
E.1.2 | Term | Lymphoma |
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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 evaluate the overall tumor response rate of GM-CSF associated with RCHOP (overall objective complete and partial response rates) in patients with follicular lymphoma with no prior treatment
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E.2.2 | Secondary objectives of the trial |
•To evaluate time to progression (TTP) •To evaluate overall survival (OS) •To evaluate the duration of response (DR) •Time to next treatment (TTNT) •To evaluate the safety profile of GM-CSF in association with RCHOP chemotherapy •To evaluate FcRs polymorphisms influence on clinical response •To monitor FcRs expressing cells in peripheral blood along the treatment •To monitor the molecular biological marker bcl-2 (translocation t(14;18) in peripheral blood and bone marrow (quantitative PCR assay)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Histologically confirmed follicular lymphoma grade 1, 2 or 3a (biopsy ≤ 4 months). •Patients previously untreated (including treatments with steroids and radiation therapy) •Bulky disease at study entry according to the GELF criteria: Nodal or extranodal mass > 7cm in its greater diameter Involvement of at least 3 nodal sites (each with a diameter greater than 3 cm) B symptoms Elevated serum LDH or β2-microglobulin Splenic enlargement Compressive syndrome Pleural/peritoneal effusion •Age must be > 18 years. •Performance status < 2 on the ECOG scale (see Appendix 0 page 40). •Adequate hematological function (unless those abnormalities are related to lymphoma extension) within 28 days prior to registration, including: Hemoglobin ≥ 8.0 g/dL (5.0 mmol/L) Absolute neutrophil count (ANC) ≥ 1.0x109/L Platelet count ≥ 100x109/L •Women are not breast feeding, are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 12 months thereafter. Men agree not to father a child during participation in the trial and during the 12 months thereafter. •Patients with at least one measurable lesion •Having previously signed a written informed consent form. |
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E.4 | Principal exclusion criteria |
•Transformation to high-grade lymphoma (secondary to “low-grade” follicular lymphoma). •Grade 3b follicular lymphoma. •Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis). •Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone. •Patients with prior or concomitant malignancies except nonmelanoma skin cancer or adequately treated in situ cervical cancer. •Major surgery (excluding lymph node biopsy) within 28 days prior to registration. •Poor renal function: Serum creatinine > 2.0 mg/dL (197 μmol/L), •Poor hepatic function: total bilirubin > 2.0 mg/dL (34 μmol/L), AST (SGOT) > 3 x the upper limit of normal unless these abnormalities are related to lymphoma. •Known HIV infection or active HBV or HCV infection ≤ 4 weeks at registration. •Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease, heart failure). Judgment is up to the investigator. •Life expectancy < 6 months •Known sensitivity or allergy to murine products •Treatment within a clinical trial within 30 days prior to trial entry •Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
•Overall response rate (including CR and PR) after induction as defined by international criteria ([1] Appendix 0 page 39) |
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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 | No |
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.8.3 |
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.8.5 | 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 | Information not present in EudraCT |
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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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 | |
E.8.9.1 | In the Member State concerned days | |