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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

Phase 2
Conditions
Lymphoma
Interventions
Registration Number
NCT02049580
Lead Sponsor
Istituto Clinico Humanitas
Brief 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
47
Inclusion Criteria

Not provided

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RIC regimenThiotepaThiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation.
RIC regimenFludarabineThiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation.
RIC regimenCyclophosphamideThiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation.
Primary Outcome Measures
NameTimeMethod
Procedure activity1 year

1-year Progression Free Survival (PFS) to evaluate the activity of the procedure (taking into account an excess of toxicity). It is assumed that at 1-year a proportion of patients progression free of 20% or lower will be considered to be clinically unworthy, whereas a proportion of 40% or higher will be assumed to be of potential interest.

Secondary Outcome Measures
NameTimeMethod
Neutrophils recovery1 year

Neutrophils will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated

Platelets recovery1 year

Platelets will be measured at different time points of increasing lenght up to 1 year after transplant and then if clinically indicated

Incidence of graft failure1 year
Cumulative incidence of acute and chronic GVHD1 year
Incidence of infections1 year

Possible infections will be monitored for a time period of 1 year post-transplantation and then if clinically required

Cumulative incidence of relapse/progression1 year
Treatment related mortality (TRM)1 year
Immunological reconstitution1 year

T, B and NK subsets will be analysed in deep using cytofluorimetry and functional tests.

Trial Locations

Locations (1)

Istituto Clinico Humanitas

🇮🇹

Rozzano, MI, Italy

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