Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Fundación Pública Andaluza Progreso y Salud
Sponsor:
Collaborator:
Iniciativa Andaluza en Terapias Avanzadas
Information provided by (Responsible Party):
Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT01751243
First received: December 13, 2012
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

Therapeutic exploratory study to evaluate safety, open, nonrandomized, multicentre, prospective, of cohort of patients who will receive different doses of allo-depleted lymphocytes .

This project joins in this pioneering worldwide initiative with its own technology based on the use of proteasome inhibitors in vitro, which advantages are, over other methods described, the continuing viability of regulatory T cells and the use of a product to generate allo-depletion that, contrary to those reported by other research groups, it does not pose problems from the point of view of its use or toxicity as we employ a drug widely used clinically by intravenous administration.


Condition Intervention Phase
Transplant-Related Hematologic Malignancy
Other: Allo-depleted lymphocyte infusion
Other: Haploidentical transplantation of hematopoietic progenitors
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies.

Resource links provided by NLM:


Further study details as provided by Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Number of adverse events and serious adverse events after allo-depleted lymphocyte infusion in vitro. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of acute and chronic GVHD [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group 0
Haploidentical transplantation of hematopoietic progenitors
Other: Haploidentical transplantation of hematopoietic progenitors
Haploidentical transplantation of hematopoietic progenitors without subsequent infusion of allo-depleted lymphocytes.
Experimental: Group 1
Allo-depleted lymphocyte infusion dose: 1x105 CD3/Kg
Other: Allo-depleted lymphocyte infusion
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;
Experimental: Group 2
Allo-depleted lymphocyte infusion dose: 3x105 CD3/Kg
Other: Allo-depleted lymphocyte infusion
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;
Experimental: Group 3
Allo-depleted lymphocyte infusion dose: 5x105 CD3/Kg
Other: Allo-depleted lymphocyte infusion
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;
Experimental: Group 4
Allo-depleted lymphocyte infusion dose: 1x106 CD3/Kg
Other: Allo-depleted lymphocyte infusion
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;
Experimental: Group 5
Allo-depleted lymphocyte infusion dose: 3x106 CD3/Kg
Other: Allo-depleted lymphocyte infusion
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   16 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01751243

Contacts
Contact: Ana Cardesa 0034 955019040 ana.cardesa@juntadeandalucia.es

Locations
Spain
University Hospital Reina Sofia Not yet recruiting
Cordoba, Spain, 14004
Contact: Antonio Torres, MD         
Principal Investigator: Mª Carmen Martín Calvo, MD         
University Hospital Carlos Haya Not yet recruiting
Malaga, Spain, 29010
Contact: Mª Angeles Cuesta, MD         
Principal Investigator: Mª Angeles Cuesta, MD         
University Hospital de Salamanca Not yet recruiting
Salamanca, Spain, 37007
Contact: Lucia Lopez-Corral, MD         
Principal Investigator: Lucia Lopez-Corral, MD         
University Hospital Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Jose-Antonio Perez-Simón, MD, PhD    955 013261      
Principal Investigator: Jose-Antonio Perez-Simón, MD         
Sponsors and Collaborators
Fundación Pública Andaluza Progreso y Salud
Iniciativa Andaluza en Terapias Avanzadas
Investigators
Principal Investigator: Jose-Antonio Perez-Simón, MD, PhD University Hospital Virgen del Rocío
Principal Investigator: Antonio Torres, MD, PhD University Hospital Reina Sofía
Principal Investigator: Lucía Lopez-Corral, MD, PhD University Hospital de Salamanca
Principal Investigator: Mª Ángeles Cuesta, MD, PhD University Hospital Carlos Haya
  More Information

Additional Information:
No publications provided

Responsible Party: Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01751243     History of Changes
Other Study ID Numbers: ALODEPLETE
Study First Received: December 13, 2012
Last Updated: December 20, 2013
Health Authority: Spain: Ethics Committee

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 16, 2014