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