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Reduced Intensity Conditioning (RIC) Regimen and Post-transplant Cyclophosphamide in Haploidentical Bone Marrow Transplantation in in Patients With Poor Prognosis Lymphomas
Conditions
Lymphoma
Conditions: official terms
Lymphoma
Conditions: Keywords
lymphoma
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: Fludarabine
Type: Drug
Name: Cyclophosphamide
Type: Drug
Overall Status
Recruiting
Summary
Study to test feasibility and efficacy of T-replete Bone Marrow (BM), infused after a RIC regimen and post-transplantation Cyclophosphamide (Cy), in patients with poor prognosis lymphomas.
Detailed Description
Allogeneic stem cell transplantation (ALLO) is the treatment of choice for many hematological diseases. However, HLA identical donor (sibling or unrelated) is available for 50-60% of patients and alternative donors are needed. Haploidentical donors have been used for many years, mostly after extensive T-cell depletion of peripheral stem cell, to avoid Graft Versus Host Disease (GVHD). Recently, promising data have been reported with haploidentical transplantation using T-replete bone marrow (BM) and high-dose cyclophosphamide (Cy) post-transplantation. However, the conditioning regimen did not contain drugs active against hemopathies, enhancing the relapse risk.
In this study, the investigators want to test the feasibility and efficacy of T-replete BM, infused after a RIC regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases.
The RIC regimen consisted of modified regimen used in different studies conducted in Italy on behalf GITMO.
In this study, the investigators want to test the feasibility and efficacy of T-replete BM, infused after a RIC regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases.
The RIC regimen consisted of modified regimen used in different studies conducted in Italy on behalf GITMO.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 70 Years
Minimum Age: 18 Years
Gender: Both
Criteria: - Signed and dated IEC-approved informed consent
- Age ≥ 18-70 years old.
- Performance Status Karnofsky ≥ 80% (see appendix B)
- HLA typing will be performed at high resolution (allele level) for the HLA-A, HLA -B, HLA Cw, HLA-DRB1, and HLA-DQB1 loci. A minimum match of 5/10 is required. An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant.
- The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Patients with lymphoma (any histology) relapsed after high dose chemotherapy and in partial remission, complete remission or stable disease after the last CT line.
1. Hodgkin's lymphoma: Patients refractory to at least 2 CT lines, and included in tandem auto-allo program
2. Diffuse large B cell lymphoma: Refractory to second line salvage chemotherapy (patients in partial remission, stable disease or progressive). These patients have to be in partial remission, complete remission or stable disease after one o more further CT line.
3. Peripheral T cell lymphoma: Patients failing to achieve a complete remission after first line CT.
4. Low grade lymphomas (follicular and non follicular: Patients refractory to rituximab containing regimens. Patients relapsing after at least 2 lines CT. The duration of remission should be < 1 year.
5. Chronic lymphatic leukemia: Patients with refractory or relapsing (response duration < 1 year) disease after R-Fludarabine CT
6. Mantle cell lymphoma: Patients relapsing or refractory after first line conventional CT.
- Absence of HLA identical sibling and 10/10 unrelated donor
- Patients with adequate physical function as measured by:
Cardiac: Left ventricular ejection fraction at rest must be ≥ 40% Hepatic: Bilirubin ≤ 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase ≤ 5 x ULN.
Renal: Creatinine clearance or GFR ≥ 50 mL/min/1.73 m2. Pulmonary: FEV1, FVC, DLCO ≥ 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation ≥ 92% on room air.
Exclusion Criteria:
- Presence of HLA-matched, related donor (HLA-A, -B, -DRB1)
- Presence of matched unrelated donor (10/10), available on time.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection
- Evidence of progression of clinical symptoms or radiologic findings.
- Prior allogeneic hematopoietic stem cell transplant.
- Central Nervous System (CNS) lymphoma localization
- Age ≥ 18-70 years old.
- Performance Status Karnofsky ≥ 80% (see appendix B)
- HLA typing will be performed at high resolution (allele level) for the HLA-A, HLA -B, HLA Cw, HLA-DRB1, and HLA-DQB1 loci. A minimum match of 5/10 is required. An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant.
- The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
- Patients with lymphoma (any histology) relapsed after high dose chemotherapy and in partial remission, complete remission or stable disease after the last CT line.
1. Hodgkin's lymphoma: Patients refractory to at least 2 CT lines, and included in tandem auto-allo program
2. Diffuse large B cell lymphoma: Refractory to second line salvage chemotherapy (patients in partial remission, stable disease or progressive). These patients have to be in partial remission, complete remission or stable disease after one o more further CT line.
3. Peripheral T cell lymphoma: Patients failing to achieve a complete remission after first line CT.
4. Low grade lymphomas (follicular and non follicular: Patients refractory to rituximab containing regimens. Patients relapsing after at least 2 lines CT. The duration of remission should be < 1 year.
5. Chronic lymphatic leukemia: Patients with refractory or relapsing (response duration < 1 year) disease after R-Fludarabine CT
6. Mantle cell lymphoma: Patients relapsing or refractory after first line conventional CT.
- Absence of HLA identical sibling and 10/10 unrelated donor
- Patients with adequate physical function as measured by:
Cardiac: Left ventricular ejection fraction at rest must be ≥ 40% Hepatic: Bilirubin ≤ 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase ≤ 5 x ULN.
Renal: Creatinine clearance or GFR ≥ 50 mL/min/1.73 m2. Pulmonary: FEV1, FVC, DLCO ≥ 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation ≥ 92% on room air.
Exclusion Criteria:
- Presence of HLA-matched, related donor (HLA-A, -B, -DRB1)
- Presence of matched unrelated donor (10/10), available on time.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection
- Evidence of progression of clinical symptoms or radiologic findings.
- Prior allogeneic hematopoietic stem cell transplant.
- Central Nervous System (CNS) lymphoma localization
Location
Istituto Clinico Humanitas
Rozzano, MI, Italy
Status: Recruiting
Contact: Luca Castagna, MD - +39028224 - luca.castagna@humanitas.it
Start Date
July 2013
Completion Date
November 2016
Sponsors
Istituto Clinico Humanitas
Source
Istituto Clinico Humanitas
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page