Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies.
16 Years
50 Years
Both
Transplant-Related Hematologic Malignancy
Trial Information
Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies.
The main objective of the study is to determine the safety of transplantation of
hematopoietic progenitors from haploidentical donor with in vitro allo-depleted lymphocyte
infusion.
Secondary objectives:
- To assess the immune reconstitution pre and post-infusion of allo-depleted lymphocytes.
- To analyze the incidence of infections (CMV and aspergillus) post-transplant.
- To analyze the impact of acute and chronic graft-versus-host disease (GVHD).
- To optimize the dose of allo-depleted lymphocytes to reconstitute an immune response
against pathogens without causing GVHD.
- To assess the rate of graft and myeloid and platelet engraftment time.
- To assess the rate of relapses, event-free survival and overall survival. It is hoped
to recruit 20 clinically evaluable patients for safety purpose.
The inclusion period is not more than 2 ½ years. Study duration shall not exceed three years
from the inclusion of the first patient. The minimum follow-up of patients is 6 months after
transplantation.
The first 5 patients (group 0) will receive haploidentical transplantation of hematopoietic
progenitors without subsequent infusion of allo-depleted lymphocytes and then in cohorts of
3 patients, infuse +4 post-transplant day at doses of: 1x105 cluster of differentiation 3
(CD3)/kg(group 1), 3x105 CD3/kg (group 2), 5x105 CD3 / kg (group 3), 1x106 CD3/kg (group 4)
and 3x106 CD3/kg (group 5).
Donor: it is performed one leukapheresis at least 30 days (4 weeks) prior to the scheduled
progenitors infusion (day 0), in order to obtain effector T cells.
Inclusion Criteria:
- Adult patients aged between 16 and 50 years.
- Diagnosed as Hematological malignancy candidates to allogeneic transplant lacking of
related or unrelated suitable donor (is more than one Human leukocyte antigen (HLA)
mismatched over 8 antigens) and who don't have a cord with an adequate cellularity.
The minimum period of search to be able to include the patient in the trial,
currently considering the medium to find a suitable donor to be 2 months, it is set
to 10 weeks, although in specific situations in which the responsible physician
considers that the patient has a high risk of relapse, it may be proceed with
inclusion before that period. These cases will be assessed individually with the
trial coordinator.
Exclusion Criteria:
- General condition> Eastern Cooperative Oncology Group (ECOG) scale 2.
- Left Ventricular ejection fraction (LVEF) <39%.
- Diffusion capacity of lung for carbon monoxide (DLCO) and forced vital capacity (FVC)
<39% of the theoretical values.
- Impaired liver function (total bilirubin higher than 2 mg / dL and / or transaminases
higher than 3 times the normal maximum.
- Creatinine clearance <50 mL / minute.
- Presence of symptomatic heart, liver cirrhosis or chronic active hepatitis.
- Active tuberculosis.
- Serious diseases which prevent chemotherapy treatments.
- Associated neoplasias (active neoplasias which, according to the opinion of the
investigator and the sponsor, could jeopardize patient safety).
- Presence of associated psychiatric pathology.
- HIV infection.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of adverse events and serious adverse events after allo-depleted lymphocyte infusion in vitro.
Outcome Time Frame:
6 months
Safety Issue:
Yes
Principal Investigator
Jose-Antonio Perez-Simón, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Hospital Virgen del Rocío
Authority:
Spain: Ethics Committee
Study ID:
ALODEPLETE
NCT ID:
NCT01751243
Start Date:
January 2013
Completion Date:
January 2016
Related Keywords:
- Transplant-Related Hematologic Malignancy
- Neoplasms
- Hematologic Neoplasms
Name | Location |
|---|
