Thiotepa, Busulfan and Fludarabin for pt With Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas — TBF  

B-cell Lymphoma Refractory Clinical Trial

Official title: Allogeneic Transplantation After a Conditioning With Thiotepa, Busulfan and Fludarabin for the Treatment of Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas: a Phase II Multi-Center Trial

Status Recruiting

Clinical Trial Summary

The purpose of this study is to evaluate progression free survival, transplant-related morbidity (TRM) at day +100 and at +365, overall survival and incidence of acute and chronic GVHD in refractory/early relapsed aggressive B-cell non Hodgkin lymphomas patients treated with allogeneic Transplantation after a conditioning with Thiotepa, Busulfan and fludarabin.

Clinical Trial Description

In the present study, it is hypothesised that patients with aggressive B cell lymphomas refractory to or relapsed early (within 12 months) after the completion of standard first-line immunoProtocol TBF2012 Version 1, 20 Nov 2012 9 chemotherapy can benefit from de-bulking salvage therapy (i.e. R-DHAP + bortezomib) followed by an allograft to improve progression-free survival.

Patient inclusion criteria

• Patients with refractory/relapsed aggressive B-cell non Hodgkin lymphomas after frontline therapy.

• Patients with stable disease or partial or complete remission (PET-negative) after salvage therapy

• Patients younger than 65 years old

• A fully HLA-identical sibling or matched unrelated donor is available. Patients with one antigen mismatched donors can be considered

• Patient must be competent to give consent

Patient exclusion criteria

• Patients treated with an autologous transplant as salvage therapy

• Patients with progressive lymphomas despite conventional therapies

• Patients with progressive lymphomas despite conventional therapies

• Uncontrolled CNS involvement with disease

• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment

• Females who are pregnant or breastfeeding

• Organ dysfunction defined as follows:

• Cardiac function: ejection fraction <30% or uncontrolled cardiac failure

• Pulmonary: DLCO <40% predicted

• Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4 the upper limit of normal

• Renal: creatinine clearance <50 cc/min (24 hour urine Protocol TBF2012 Version 1, 20 Nov 2012 6 collection)

• Karnofsky performance score < 60%

• Patients with poorly controlled hypertension despite multiple antihypertensives

• Documented fungal disease that is progressive despite treatment

• Viral infections: HIV positive patients.

• Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded.

• Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result

• Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.

• Patients with active non-hematologic malignancies (except nonmelanoma skin cancers).

• Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a >20% risk of disease recurrence. Donor inclusion criteria:

• Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.

• No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.

• Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:

• Age < 18 years.

• Identical twin.

• Pregnancy.

• Infection with HIV.

• Inability to achieve adequate venous access.

• Known allergy to filgrastin (G-CSF).

• Current serious systemic illness.

Donor inclusion criteria:

• Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.

• No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.

• Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:

• Age < 18 years.

• Identical twin.

• Pregnancy.

• Infection with HIV.

• Inability to achieve adequate venous access.

• Known allergy to filgrastin (G-CSF).

• Current serious systemic illness.

Donor inclusion criteria:

• Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation. One antigen HLAmismatched (9/10 match) donors will also be considered.

• No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 10-12 μg/kg of body weight.

• Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian). Donor exclusion criteria:

• Age < 18 years.

• Identical twin.

• Pregnancy.

• Infection with HIV.

• Inability to achieve adequate venous access.

• Known allergy to filgrastin (G-CSF).

• Current serious systemic illness. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Lymphoma Refractory
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

• NCT number: NCT01786018
• Study type: Interventional
• Source: Azienda Ospedaliera San Giovanni Battista
• Contact: Benedetto Bruno, MD
• Phone: +390116336728
• Email: benedetto.bruno@unito.it
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2013
• Completion date: February 2015