Thiotepa, Busulfan and Fludarabin for pt With Refractory/Early Relapsed Aggressive B-cell Non Hodgkin Lymphomas
- Conditions
- B-cell Lymphoma Refractory
- Interventions
- Drug: FludarabinProcedure: transplant (HCT)Radiation: CytoreductionDrug: ImmunosuppressionProcedure: Collection and infusions of Donor PBSC
- Registration Number
- NCT01786018
- Lead Sponsor
- Azienda Ospedaliera San Giovanni Battista
- Brief 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 42
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 Thiotepa * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 transplant (HCT) * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Fludarabin * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Cytoreduction * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Collection and infusions of Donor PBSC * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Immunosuppression * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Busulfan * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Methotrexate * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 Cyclosporine * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2) 1 ATG * Thiotepa 5 mg/kg/day on days -7, -6 (Total Dose 10 mg/kg) * Busulfan (i.v.) 3.2 mg/kg on days -5,-4,-3 (Total Dose 9.6 mg/kg) * Fludarabin: 50 mg/m2/day on days -5,-4,-3 (Total Dose 150 mg/m2)
- Primary Outcome Measures
Name Time Method Progression free survival 2 years
- Secondary Outcome Measures
Name Time Method Incidence of acute and chronic GVHD 2 years Transplant-related morbidity (TRM) at day +100 and at +365 1 year Overall survival 2 years
Trial Locations
- Locations (1)
Città della Salute e della Scienza di Torino
🇮🇹Torino, Italy