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Trial Title:
Reduced Intensity Conditioning (RIC) Regimen and Post-transplant Cyclophosphamide in Haploidentical Bone Marrow Transplantation in in Patients With Poor Prognosis Lymphomas
NCT ID:
NCT02049580
Condition:
Lymphoma
Conditions: Official terms:
Lymphoma
Cyclophosphamide
Thiotepa
Fludarabine
Conditions: Keywords:
lymphoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Thiotepa
Description:
Thiotepa (10 mg/kg /day) will be administered every 12 h, at day -6
Arm group label:
RIC regimen
Other name:
Tepadina
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
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
Arm group label:
RIC regimen
Other name:
Fludara
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
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).
Arm group label:
RIC regimen
Other name:
Endoxan
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Istituto Clinico Humanitas
Address:
City:
Rozzano
Zip:
20089
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Luca Castagna, MD
Phone:
+39028224
Phone ext:
4587
Email:
luca.castagna@humanitas.it
Investigator:
Last name:
Luca Castagna, MD
Email:
Principal Investigator
Start date:
July 2013
Completion date:
November 2016
Lead sponsor:
Agency:
Istituto Clinico Humanitas
Agency class:
Other
Source:
Istituto Clinico Humanitas
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02049580