Pixantrone (BBR 2778) versus Other Chemotherapeutic Agents for Third-line Single Agent Treatment of Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma: A Randomized, Controlled, Phase III Comparative Trial - N/A

Conditions: on-Hodgkin's Lymphoma

Registration Number: EUCTR2004-000480-10-ES

Lead Sponsor: CELL THERAPEUTICS INC. (EUROPE)-SEDE SECONDARIA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 320

Inclusion Criteria

All of the following characteristics are required for study eligibility:
1. Histologically confirmed aggressive [de novo or transformed] NHL according to REAL/WHO classification. The histological specimen used to determine eligibility must be the most recently obtained specimen. Lymph node biopsy slides or tissue blocks suitable for review must be available.
- follicular lymphoma – grade III
- transformed indolent lymphoma
- diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, primary effusion lymphoma (includes previously called immunoblastic lymphoma)
- peripheral T-cell lymphoma, not otherwise characterized
(encompasses diffused mixed cell lymphoma)
- anaplastic large cell lymphoma, T/null cell, primary systemic type
Note: patients with any Ann Arbor stage, International Prognostic Index (IPI) score or bone marrow status are eligible.
2. Patients must have received rituximab in prior regimens in those countries where it is available and when neoplastic cells express CD20.
3. At least one objectively measurable lesion as demonstrated by CT, spiral CT, or MRI and plain radiograph of the chest (chest x-ray, for chest lesions only) that can be followed for response as target lesion. Patients with the following sites of disease are NOT eligible:
- Patients with only skin lesions or only palpable lymph nodes.
- Patients with spleen or bone marrow as only site of disease.
4. Relapse after 2 or more prior regimens of chemotherapy, including:
- first line treatment with a standard anthracycline-containing regimen such as CHOP or equivalent
- at least one additional combination chemotherapy regimen. High dose chemotherapy or chemoradiotherapy with autologous stem cell support counts as one prior regimen.
5. Patients must be sensitive to anthracycline/anthracenedione. Sensitive is defined as:
- Previously responded to anthracycline/anthracenedione, and
- Relapsed after a response duration =6 months.
6. Age =18 years.
7. ECOG performance status of =2.
8. Life expectancy =3 months according to investigator opinion.
9. Hb = 8g/dL, neutrophils =1.5 x 10exp9/L and platelets =100 x10exp9/L. If there is bone marrow involvement then neutrophils >0.5 x 10exp9/L and platelets >50 x 10exp9/L is acceptable.
10. Serum bilirubin =1.5 x the institution’s upper limit normal (ULN) and creatinine
= 1.5 ULN and alkaline phosphatase = 2.0 x the institution’s ULN and AST or ALT
= 2.0 x the institution’s ULN. If hepatic involvement by lymphoma is present, AST or ALT may be = 5.0 x the institution’s ULN.
11. Patients previously treated with one of the comparative agents must be sensitive to that agent, if it will be used in this trial. Sensitive is defined as:
- Previously responded to that agent, and
- Relapsed after a response duration = 6 months.
12. Patients must have recovered from all acute toxicities from prior therapy (except alopecia and grade 1 peripheral neuropathy).
13. LVEF =50% determined by MUGA scan.
14. Ability to comply with the visit schedule and assessments required by the protocol.
15. Signed approved informed consent, with understanding of study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

None of the following characteristics may be present:
1. Prior treatment with a cumulative dose of doxorubicin or equivalent (see section 17.2) exceeding 450 mg/m² according to the following calculation index:
X/450 + Y/160 < 1
where X is the doxorubicin dose in mg/m² and Y the mitoxantrone dose in mg/m².
2. Prior allogenic stem cell transplant.
3. Histological diagnosis of Burkitt lymphoma, lymphoblastic lymphoma or Mantle cell lymphoma.
4. Active CNS lymphoma.
5. HIV-related lymphoma.
6. Any chemotherapy, radiotherapy, or other anticancer treatment (including corticosteroid, 10 or more mg/day of prednisone or equivalent) within the 4 weeks before randomization.
7. Major thoracic and/or abdominal surgery within the 4 weeks before randomization from which the patient has not fully recovered. Patients who have had minor surgery may be enrolled after a =1 week recovery period.
8. Clinically significant cardiovascular abnormalities (equal to NYHA grade II - IV), myocardial infarction within the prior 6 months, severe arrhythmia or uncontrolled hypertension.
9. Serious (NCI CTCAE grade 3-4) intercurrent infection at randomization or deep seated or systemic mycotic infections.
10. History of or clinical symptoms suggesting HIV, HBV or HCV infection. Patients with seropositivity presumed to be due to prior vaccination against Hepatitis B virus will not be excluded.
11. History of another malignancy except cured basal cell carcinoma of skin or carcinoma in–situ of uterine cervix.
12. Any condition which, in the judgment of the Investigator, would place the subject at undue risk, interfere with the results of the study, or make the subject otherwise unsuitable.
13. Other investigational drug study within 30 days before randomization. Patient must have recovered from all side effects of other investigational therapy.
14. Pregnant women or nursing mothers.
15. Potentially fertile men and women not willing to use adequate contraception during the study and for 6 months after the last day of study drug administration.
16. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary study objective is to compare the efficacy of BBR 2778 to a selection of single agents in terms of complete response (CR) and unconfirmed complete response (CRu) rate according to the report of the international workshop to standardize response criteria for Non Hodgkin's Lymphoma;Secondary Objective: Secondary objectives are to compare efficacy as demonstrated by overall survival, CR and CRu rate in histologically confirmed patients, objective overall response lasting at least 4 months, and time to progression. Additional pre specified analyses will be overall response rate, time to initial response, time to complete response, duration of response, dose intensity, cardiac function, and safety;Primary end point(s): Complete response (CR) and unconfirmed Complete response (CRu) rate: The total proportion of patients with CR or CRu.CR and CRu will be defined according to the report of the international workshop to standardize response criteria for NHL.<br>

Secondary Outcome Measures

Name	Time	Method

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