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CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene
This study is currently recruiting participants.
Verified August 2011 by Baylor College of Medicine

First Received on July 3, 2008.   Last Updated on August 12, 2011   History of Changes
Sponsor: Baylor College of Medicine
Collaborators: Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00710892
  Purpose

This Phase I trial is designed to determine the number of suicide gene-modified allodepleted donor lymphocytes that can be given to recipients of haploidentical stem cell transplants resulting in 25% or less developing grade 3 or 4 GVHD.

The exact number of patients required for the study is not known as this is a Phase I trial but the investigators will require anywhere between 3 to 18 patients for the whole study. The accrual rate is expected to be about 8 patients per year. There is no randomization and no control group.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
Biological: Allodepleted T Cells
Phase I

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: CASPALLO: Allodepleted T Cells Transduced With Inducible Caspase 9 Suicide Gene After Haploidentical Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • To determine the number of suicide gene-modified allodepleted donor lymphocytes that can be given to recipients of haploidentical stem cell transplants that will result in a rate of Grade III/IV GVHD of 25% or less. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To evaluate the biological and clinical effects of administration of AP1903, a dimerizer used to activate the suicide gene mechanism, in patients who develop Grade 3 or 4 GVHD. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To analyze the contribution of the gene-modified cells to immune reconstitution in these patients by measuring their survival, persistence and expansion [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  • To measure the overall and disease free survival, at 100 days and at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: December 2008
Estimated Study Completion Date: August 2028
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1-3 Biological: Allodepleted T Cells

Dose Level 1: 1 x 10exp6 T cells/Kg Dose Level 2: 3 x 10exp6 T cells/Kg Dose Level 3: 1 x 10exp7 T cells/Kg

Patients may be enrolled on the next dose level of T cells when all patients on the previous dose level have reached Day 40 days following initial -T cell infusion without unacceptable toxicity.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

At the time of transplant:

Patients (up to 65 years of age) with:

  1. ALL or high grade NHL that is Stage III or IV and has relapsed or is considered to be primary refractory disease
  2. Myelodysplastic syndrome
  3. AML after first relapse or with primary refractory disease
  4. CML
  5. Hemophagocytic lymphohistiocytosis (HLH), familial hemophagocytic lymphohistiocytosis (FLH), viral-associated hemophagocytic syndrome (VAHS), patients with Severe chronic active Epstein Barr virus infection (SCAEBV) with predilection for T or NK cell malignancy, X-linked lymphoproliferative disease (XLP);

Lack of suitable conventional donor (i.e. 5/6 or 6/6 related or 5/6 or 6/6 unrelated donor) or presence of a rapidly progressive disease not permitting time to identify an unrelated donor.

Inclusion Criteria at time of allodepleted T cell infusion:

  1. Engrafted with ANC greater than 500
  2. Must have greater than or equal to 50% donor chimerism in either peripheral blood or bone marrow or relapse of their original disease
  3. Life expectancy greater than 30 days
  4. Lansky/Karnofsky scores greater than 60
  5. Absence of severe renal disease (Creatinine greater than 2X normal for age)
  6. Absence of severe hepatic disease (direct bilirubin greater than 2mg/dl, or SGOT greater than 200
  7. O2 sat greater than 94% on room air
  8. Patient/Guardian able to give informed consent

Exclusion Criteria:

At the time of transplant: - Pregnant*

At the time of allodepleted T cell infusion:

  • GVHD
  • Severe intercurrent infection
  • Pregnant*
  • Other investigational drugs in the prior 30 days

    • Pregnancy test only required for at risk individuals, defined as female patients of childbearing potential who has received a reduced intensity conditioning regimen.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00710892

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Malcolm Brenner, MB, PhD     832-824-4671     mkbrenne@txccc.org    
Contact: Helen Heslop, MD     832-824-4662     heheslop@txccc.org    
Principal Investigator: Malcolm Brenner, MB, PhD            
Sub-Investigator: George Carrum, MD            
Sub-Investigator: Bambi J Grilley            
Sub-Investigator: Robert A Krance, MD            
Sub-Investigator: Helen E Heslop, MD            
Sub-Investigator: Cliona M Rooney, MD            
Sub-Investigator: Adrian P Gee, MD            
Sub-Investigator: Stephen M Gottschalk, MD            
Sub-Investigator: Kathryn S Leung, MD            
Sub-Investigator: Gianpietro Dotti, MD            
Sub-Investigator: Catherine M Bollard, MD            
Sub-Investigator: Nabil M Ahmed, MD            
Sub-Investigator: Alana A Kennedy-Nasser, MD            
Sub-Investigator: Antonio Distasi, MD            
Sub-Investigator: Rammurti T Kamble, MD            
Sub-Investigator: Hao Liu            
Sub-Investigator: Caridad Martinez, MD            
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD     713-394-6250     gcarrum@bcm.edu    
Sub-Investigator: George Carrum, MD            
Sub-Investigator: Malcolm Brenner, MD, PhD            
Sub-Investigator: Helen E Heslop, MD            
Sub-Investigator: Rammurti Kamble, MD            
Texas Children's Cancer Center GCRC Recruiting
Houston, Texas, United States, 77030
Contact: Helen Heslop, MD     832-824-4662     heheslop@txccc.org    
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Malcolm K Brenner, MD     832-824-4671     mbrenner@bcm.tmc.edu    
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Malcolm Brenner, MD Baylor College of Medicine
  More Information

No publications provided by Baylor College of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Malcolm Brenner, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00710892     History of Changes
Other Study ID Numbers: 21580-CASPALLO
Study First Received: July 3, 2008
Last Updated: August 12, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
suicide gene-modified allodepleted donor lymphocytes
given to recipients of haploidentical stem cell transplants
Stage III
Stage IV
Myelodysplastic syndrome
AML after first relapse
primary refractory disease
CML
Hemophagocytic lymphohistiocytosis (HLH)
familial hemophagocytic lymphohistiocytosis (FLH)
viral-associated hemophagocytic syndrome (VAHS)
Severe chronic active Epstein Barr virus infection (SCAEBV)
T or NK cell malignancy
X-linked lymphoproliferative disease (XLP)

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphohistiocytosis, Hemophagocytic
Lymphoma
Lymphoma, Non-Hodgkin
Suicide
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Self-Injurious Behavior
Behavioral Symptoms

ClinicalTrials.gov processed this record on February 09, 2012