Clinical trial NCT02049580: Reduced Intensity Conditioning (RIC) Regimen and Post-transplant Cyclophosphamide in Haploidentical Bone Marrow Transplantation in in Patients With Poor Prognosis Lymphomas
Official title: Multi-center, Phase II Study to Assess the Safety and Efficacy of Haploidentical Bone Marrow Transplantation Using Reduced Intensity Conditioning(RIC)Regimen and Post-transplant Cyclophosphamide,in Patients With Poor Prognosis Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma
Keywords: lymphoma
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
First posted: 2014-01-30
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Procedure activity
timeFrame: 1 year
Secondary outcomes:
measure: Neutrophils recovery
timeFrame: 1 year
measure: Platelets recovery
timeFrame: 1 year
measure: Incidence of graft failure
timeFrame: 1 year
measure: Cumulative incidence of acute and chronic GVHD
timeFrame: 1 year
measure: Incidence of infections
timeFrame: 1 year
measure: Cumulative incidence of relapse/progression
timeFrame: 1 year
measure: Treatment related mortality (TRM)
timeFrame: 1 year
measure: Immunological reconstitution
timeFrame: 1 year
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
Study officials:
affiliation: Istituto Clinico Humanitas
name: Luca Castagna, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, Gandolfi S, Tentorio P, Sarina B, Timofeeva I, Santoro A, Carlo-Stella C, Bruno B, Carniti C, Corradini P, Gostick E, Ladell K, Price DA, Roederer M, Mavilio D, Lugli E. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood. 2015 Apr 30;125(18):2855-64. doi: 10.1182/blood-2014-11-608406. Epub 2015 Mar 5.