Multicenter Trial to Treat Patients With Relapsed/Refractory Aggressive Non Hodgkin Lymphoma

A Phase II Multicenter, Open-Label, Clinical And Pharmacokinetic Study of Aplidin® As A 1-Hour Weekly IV Infusion, in Patients With Relapsed Or Refractory Aggressive Non-Hodgkin's Lymphoma

This is a multicenter study to assess the anti-tumour activity,to investigate the safety profile and to obtain additional pharmacokinetic information for Aplidin® given as 1-hour weekly IV infusion in patients with aggressive non-Hodgkin's Lymphoma.

A Phase II Multicenter,Open-Label, Clinical And Pharmacokinetic Study Of Aplidin® As A 1-Hour Weekly IV Infusion, In Patients With Relapsed Or Refractory aggressive non-Hodgkin's Lymphoma.

Primary

• To assess the anti-tumour activity of Aplidin® given as a 1-hour weekly IV infusion, in patients with aggressive non-Hodgkin's Lymphoma, relapsing or refractory to a prior therapy.

Secondary

• To further investigate the safety profile of Aplidin® given as 1-hour weekly IV infusion in this patient population.
• To obtain additional pharmacokinetic information for Aplidin® given as 1-hour weekly IV infusion in patients with aggressive non-Hodgkin's Lymphoma.

Inclusion Criteria:

• Written informed consent
• Histologically confirmed aggressive lymphomas,
• Patient requires treatment because NHL relapses
• Measurable disease
• Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed.
• Age > 18 years.
• Performance status (ECOG) < 2
• Adequate renal, hepatic, and bone marrow function (assessed < 14 days before inclusion in the study)
• Left ventricular ejection fraction within normal limits.

Exclusion Criteria:

• Prior therapy with Aplidin®.

• Concomitant therapy with any anti-lymphoproliferative agent

• Acute lymphoblastic leukemia.

• CNS lymphoma.

• HIV-associated lymphoma.

• Prior gene therapy with viral vectors.

• More than three previous lines of systemic biological agents or chemotherapies. Wash-out periods since the end of the precedent therapy less than:

  • 6 weeks for nitroso-urea or high dose chemotherapy
  • 3 weeks for other chemotherapies or biological agents
  • 4 weeks for radiation or radionuclide therapy (6 weeks in case of prior extensive external beam radiation (more than 25% of bone marrow distribution).
  • 4 weeks for major prior surgery
  • 30 days for any investigational product
  • 4 weeks for immunosuppressive therapy after allogeneic hematopoietic stem cell transplantation.

• Pregnant or lactating women.

• Men and women of reproductive potential who are not using effective contraceptive methods

• History of another neoplastic disease. Exceptions: Non-melanoma skin cancer,cCarcinoma in situ of any site,any other cancer curatively treated and no evidence of disease for at least 10 years.

• Known cerebral or leptomeningeal involvement.

• Other relevant diseases or adverse clinical conditions

• Treatment with any investigational product in the 30 days period before inclusion in the study.

• Known hypersensitivity to Aplidin®, mannitol, cremophor EL, or ethanol

• Limitation of the patient's ability to comply with the treatment or follow-up protocol.