Study designed to assess the safety and efficacy of the use of a reduced-intensity conditioning regimen before transplantation and of cyclophosphamide after transplantation, in patients with poor prognosis lymphoma undergoing bone marrow transplant from a partially identical donor without elimination of lymphocytes T.
- Conditions
- Patients with lymphomas (any histology) relapsed after high dose chemotherapy and in complete remission or partial remission after the last CT lineMedDRA version: 14.1Level: PTClassification code 10003908Term: B-cell small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10003899Term: B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10008958Term: Chronic lymphocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10020206Term: Hodgkin's diseaseSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10034623Term: Peripheral T-cell lymphoma unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2012-005580-27-IT
- Lead Sponsor
- ISTITUTO CLINICO HUMANITAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 47
PATIENT-RELATED CRITERIA
1. Age 18-70 years old
2. Karnofsky performance score = 80%
3. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRB1, and 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.
4. 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
5. Patients with lymphomas (any histology) relapsed after high dose chemotherapy and in complete remission or partial remission after the last CT line.
a. Hodgkin’s lymphoma.
Patients refractory to at least 2 CT lines, and included in tandem auto-allo program.
b. 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 or complete remission after last CT line, including high dose chemotherapy (auto-allo program).
Transformed low grade lymphomas
c. Peripheral T cell lymphoma
Patients failing to achieve a complete remission after first line CT.
d. Low grade lymphomas (follicular and non follicular)
Patients refractory to first R-CT line.
Patients failing at least 2 lines CT - The duration of last remission should be < 1 year
e. Chronic lymphatic leukemia.
Patients with refractory or relapsing (response duration < 1 year) disease after R-Fludarabine CT
f. Mantle cell lymphoma.
Patients relapsing or refractory after first line conventional CT.
6. Absence of HLA identical sibling and 10/10 unrelated donor
7. Patients with adequate physical function as measured by:
? Hearth FEV fraction = 40%;
? Total bilirubin = 2.5 mg/dl, ALT, AST, and alkaline phosphatase all = 5 x upper limit of normal (ULN);
? Creatinine clearance or GFR by Cockroft-Gault formula = 50 mL/min/1.73m2;
? FEV1,FVC, DLCO = 50% predicted
DONOR SELECTION CRITERIA
1. Donors must be HLA-haploidentical first-degree relatives of the patient. Eligible donors include biological parents, siblings, or children, or half-siblings.
2. Age = 18 years.
3. Donors must meet the selection criteria as defined by JACIE
4. Absence of DSA (donor specific antibody against HLA antigens)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1. Presence of HLA-matched, related donor (HLA-A, -B, -DRB1)
2. Presence of matched unrelated donor (10/10), available on time.
3. Pregnancy or breast-feeding.
4. Evidence of HIV infection or known HIV positive serology.
5. Current uncontrolled bacterial, viral or fungal infection
6. Evidence of progression of clinical symptoms or radiologic findings.
7. Prior allogeneic hematopoietic stem cell transplant.
8. CNS lymphoma localization
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the activity, taking into account an excess of toxicity, of the procedure of T-replete BM infused after a reduced intensity conditioning (RIC) regimen and post-transplantation Cy, in patients with poor prognosis lymphoproliferative diseases. ;Secondary Objective: To further evaluate the efficacy and safety of the procedure;Primary end point(s): 1-year progression free survival (PFS) ;Timepoint(s) of evaluation of this end point: 1 year from the treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Neutrophil and platelet recovery <br>• Incidence of graft failure <br>• Cumulative incidence of acute and chronic GVHD <br>• Incidence of infections <br>• Cumulative incidence of relapse/progression <br>• Treatment related mortality (TRM)<br>• Immunological reconstitution ;Timepoint(s) of evaluation of this end point: controls with different frequencies in the interval between transplantation and the 1-year follow-up visit, according to clinical practice