Reduced Intensity Conditioning (RIC) Regimen and Post-transplant Cyclophosphamide in Haploidentical Bone Marrow Transplantation in in Patients With Poor Prognosis Lymphomas

NCT ID: NCT02049580

Last Updated: 2014-01-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2016-11-30

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RIC regimen

Thiotepa, Fludarabine, Cyclophosphamide pre- and post- transplantation.

Group Type: EXPERIMENTAL

Thiotepa

Intervention Type: DRUG

Thiotepa (10 mg/kg /day) will be administered every 12 h, at day -6

Fludarabine

Intervention Type: DRUG

Fludarabine (30mg/m2/day x 4 days) will be dosed according to renal function. For decreased creatinine clearance (CCr) (≤ 61 mL/min) Fludarabine dosage should be reduced as follows:

CCr 46-60 mL/min, fludarabine = 24 mg/ m2/day

Cyclophosphamide

Intervention Type: DRUG

Pre-transplantation Cyclophosphamide(Cy) 30 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -5.

Cy will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the Adjusted IBW (AIBW)

Cyclophosphamide [50 mg/kg/day IBW] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).

Interventions

Thiotepa

Thiotepa (10 mg/kg /day) will be administered every 12 h, at day -6

Intervention Type: DRUG

Fludarabine

Fludarabine (30mg/m2/day x 4 days) will be dosed according to renal function. For decreased creatinine clearance (CCr) (≤ 61 mL/min) Fludarabine dosage should be reduced as follows:

CCr 46-60 mL/min, fludarabine = 24 mg/ m2/day

Intervention Type: DRUG

Cyclophosphamide

Pre-transplantation Cyclophosphamide(Cy) 30 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -5.

Cy will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the Adjusted IBW (AIBW)

Cyclophosphamide [50 mg/kg/day IBW] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).

Intervention Type: DRUG

Other Intervention Names

Tepadina; Fludara; Endoxan

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Clinico Humanitas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luca Castagna, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Clinico Humanitas

Locations

Istituto Clinico Humanitas

Rozzano, MI, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Luca Castagna, MD

Role: CONTACT

luca.castagna@humanitas.it

+39028224 ext. 4587

Facility Contacts

Luca Castagna, MD

Role: primary

luca.castagna@humanitas.it

+39028224 ext. 4587

References

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.

Reference Type: DERIVED

PMID: 25742699 (View on PubMed)

Other Identifiers

ONC-2011-005

Identifier Type: -

Identifier Source: org_study_id