T CELL DEPLETED HEMATOPOIETIC STEM CELL TRANSPLANT POST REDUCED INTENSITY CONDITIONING AND EARLY USE OF CYCLOPHOPHAMIDE

• Conditions: -CLL patients with refractoriness to fludarabine or other chemotherapy due , Follicular lymphoma with either unfavourable cytogenetics such as complex karyotype, del17p, mutations in TP53, minus 1p- Hodgkin's Lymphoma relapsed after autologous transplantation, not elegible for immunotherapy with anti-CD30,-Multiple myeloma relapsing after autologous transplantation, with unfavourable cytogenetics in either partial or complete remission; MedDRA version: 17.0Level: HLGTClassification code 10025319Term: Lymphomas Hodgkin's diseaseSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 17.0Level: LLTClassification code 10028567Term: Myeloma, malignantSystem Organ Class: 100000004864; MedDRA version: 17.0Level: LLTClassification code 10024341Term: Leukemia lymphoidSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-003628-35-IT
• Lead Sponsor: Azienda Ospedaliero-Universitaria di Parma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-19
• Last Update Posted: 30 March 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

- age between 18 and 70; - Diagnosis according to the WHO classification: CLL patients with refractoriness to fludarabine or other chemotherapy due to the p53 loss by 17p deletion and/or TP53 mutation; Follicular lymphoma with either unfavourable cytogenetics such as complex karyotype, del17p, del 6q23-26, mutations in TP53, minus 1p; Hodgkin's Lymphoma relapsed after autologous transplantation, not elegible for immunotherapy with anti-CD30- Multiple myeloma relapsing after autologous transplantation, with unfavourable cytogenetics in either partial or complete remission. Non available
matched unrelated donor.Availability of haploidentical family donor; patients has an Eastern Cooperative Oncology Group (ECOG) performance status = 2; understands and voluntarily signs an informed consent form, skilled in adhering to the study visit schedule and other protocol requirements; creatinine clearance <1,5 or GFR >30 ml/min-
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 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

- age <18 and >70; - creatinine clearance >1,5 or GFR <30 ml/min ; -
cardiac ejection fraction <40%; - presence of second malignancies ; -
Patient has a known history of HIV seropositivity; - Patient has active
HBV hepatitis. The following categories of HBV positive patients but with
non evidence of active hepatitis may be considered for the study:
HBsAg+ and HBV DNA <2000 UI/mL (inactive carriers);HBV DNA >2000
UI/mL is criteria of exclusion, Patient is HBsAg- HBsAb+ Patient is
HBsAg- HBcAb+ Patients with HCV active hepatitis are excluded from the
study, Psychiatric problems, Inability to provide informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Stable-donor type engraftment without any post-transplant immunosuppressive treatment;Secondary Objective: - incidence of estensive acute and chronic GVHD; - transplant related mortality (TRM), - immunologic reconstitution; - Myeloid and lymphoid chimerism ; -Overall survival and progression free survival;Primary end point(s): Donor-type engraftment will be evaluated by chimerism analysis;Timepoint(s) of evaluation of this end point: At least 9-12 months, to evaluate stable chimerism

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Acute GVHD will be classified by IBMTR severity index; -Chronic GVHD will be identified according to NIH working group new global scoring system, -TRM is defined as all deaths occurred without previous relapse or progression; - Immunologic reconstitution post engraftment defined as time needed to reach and exceed 500 lymphocyte CD3+/mcL and 200 CD4+/mcL; - Myeloid and lymphoid chimerism; -Overall survival and event free survival ;Timepoint(s) of evaluation of this end point: 48 months