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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.
Verified September 2017 by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Sponsor:
ClinicalTrials.gov Identifier:
NCT01751243
First Posted: December 17, 2012
Last Update Posted: September 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Iniciativa Andaluza en Terapias Avanzadas
Information provided by (Responsible Party):
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
  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
Intervention Model: Single Group Assignment
Masking: None (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.

Further study details as provided by Andalusian Initiative for Advanced Therapies - 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 ]

Secondary Outcome Measures:
  • Incidence of acute and chronic GVHD [ Time Frame: 6 months ]

Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   16 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Andalusian Initiative for Advanced Therapies - 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:
Responsible Party: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT01751243     History of Changes
Other Study ID Numbers: ALODEPLETE
First Submitted: December 13, 2012
First Posted: December 17, 2012
Last Update Posted: September 21, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Neoplasms


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