Thiotepa, Busulfan and Fludarabin for pt With Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas
Conditions
B-cell Lymphoma Refractory
Conditions: official terms
Lymphoma - Lymphoma, B-Cell - Lymphoma, Non-Hodgkin
Conditions: Keywords
Non Hodgkin lymphomas, Allogeneic Transplantation, Thiotepa, Busulfan, Fludarabin
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Thiotepa Type: Drug
Name: Busulfan Type: Drug
Name: Fludarabin Type: Drug
Name: transplant (HCT) Type: Procedure
Name: Cytoreduction Type: Radiation
Name: Immunosuppression Type: Drug
Name: Cyclosporine Type: Drug
Name: Methotrexate Type: Drug
Name: ATG Type: Drug
Name: Collection and infusions of Donor PBSC Type: Procedure
Overall Status
Recruiting
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.
Detailed 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 18 Years
Gender: Both
Criteria: 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 >4x the upper limit of normal

- Renal: creatinine clearance <50 cc/min (24 hour urine 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 non-melanoma 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 HLA-mismatched (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 mg/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.
Location
Città della Salute e della Scienza di Torino
Torino, Italy
Status: Recruiting
Contact: Benedetto Bruno, MD - +390116336728 - benedetto.bruno@unito.it
Start Date
February 2013
Completion Date
February 2015
Sponsors
Azienda Ospedaliera San Giovanni Battista
Source
Azienda Ospedaliera San Giovanni Battista
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page