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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

Primary Purpose

Transplant-Related Hematologic Malignancy

Status
Withdrawn
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Allo-depleted lymphocyte infusion
Haploidentical transplantation of hematopoietic progenitors
Sponsored by
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transplant-Related Hematologic Malignancy

Eligibility Criteria

16 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital Reina Sofia
  • University Hospital Carlos Haya
  • University Hospital de Salamanca
  • University Hospital Virgen del Rocío

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Group 0

Group 1

Group 2

Group 3

Group 4

Group 5

Arm Description

Haploidentical transplantation of hematopoietic progenitors

Allo-depleted lymphocyte infusion dose: 1x105 CD3/Kg

Allo-depleted lymphocyte infusion dose: 3x105 CD3/Kg

Allo-depleted lymphocyte infusion dose: 5x105 CD3/Kg

Allo-depleted lymphocyte infusion dose: 1x106 CD3/Kg

Allo-depleted lymphocyte infusion dose: 3x106 CD3/Kg

Outcomes

Primary Outcome Measures

Number of adverse events and serious adverse events after allo-depleted lymphocyte infusion in vitro.

Secondary Outcome Measures

Incidence of acute and chronic GVHD

Full Information

First Posted
December 13, 2012
Last Updated
July 4, 2018
Sponsor
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Collaborators
Iniciativa Andaluza en Terapias Avanzadas
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1. Study Identification

Unique Protocol Identification Number
NCT01751243
Brief Title
Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies
Official Title
Transplantation of Hematopoietic Progenitors From Haploidentical Donor With Selective in Vitro Depletion Allo-reactive Lymphocytes in Patient With High Risk Hematological Malignancies.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Withdrawn
Study Start Date
January 2013 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Collaborators
Iniciativa Andaluza en Terapias Avanzadas

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transplant-Related Hematologic Malignancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 0
Arm Type
Placebo Comparator
Arm Description
Haploidentical transplantation of hematopoietic progenitors
Arm Title
Group 1
Arm Type
Experimental
Arm Description
Allo-depleted lymphocyte infusion dose: 1x105 CD3/Kg
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Allo-depleted lymphocyte infusion dose: 3x105 CD3/Kg
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Allo-depleted lymphocyte infusion dose: 5x105 CD3/Kg
Arm Title
Group 4
Arm Type
Experimental
Arm Description
Allo-depleted lymphocyte infusion dose: 1x106 CD3/Kg
Arm Title
Group 5
Arm Type
Experimental
Arm Description
Allo-depleted lymphocyte infusion dose: 3x106 CD3/Kg
Intervention Type
Other
Intervention Name(s)
Allo-depleted lymphocyte infusion
Intervention Description
Doses: 1x105 CD3/Kg; 3x105 CD3/Kg; 5x105 CD3/Kg; 1x106 CD3/Kg;31x106 CD3/Kg;
Intervention Type
Other
Intervention Name(s)
Haploidentical transplantation of hematopoietic progenitors
Intervention Description
Haploidentical transplantation of hematopoietic progenitors without subsequent infusion of allo-depleted lymphocytes.
Primary Outcome Measure Information:
Title
Number of adverse events and serious adverse events after allo-depleted lymphocyte infusion in vitro.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Incidence of acute and chronic GVHD
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose-Antonio Perez-Simón, MD, PhD
Organizational Affiliation
University Hospital Virgen del Rocío
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antonio Torres, MD, PhD
Organizational Affiliation
University Hospital Reina Sofía
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lucía Lopez-Corral, MD, PhD
Organizational Affiliation
University Hospital de Salamanca
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mª Ángeles Cuesta, MD, PhD
Organizational Affiliation
University Hospital Carlos Haya
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
University Hospital Carlos Haya
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
University Hospital de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
University Hospital Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://www.juntadeandalucia.es/terapiasavanzadas/
Description
Andalusian Initiative for Advanced Therapies
URL
http://www.cabimer.es
Description
Andalusian Molecular Biology and Regenerative Medicine Centre

Learn more about this trial

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

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