CD19-specific T-cell for Chronic Lymphocytic Leukemia (CLL)

This study is currently recruiting participants.
Verified March 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01653717
First received: July 27, 2012
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of T cells that can be given in combination with standard chemotherapy to patients with CLL. The safety of this combination will also be studied.

The T cells being used in this study are a type of white blood cell that will be taken from your blood and then genetically changed in a laboratory. The process of changing the DNA (the genetic material of cells) of the T cells is called a gene transfer. After the gene transfer is complete, the genetically changed T-cells will be put back into your body. These T cells may help prevent cancer cells from coming back.


Condition Intervention Phase
Advanced Cancers
Leukemia
Procedure: Leukapheresis
Drug: Fludarabine
Drug: Cyclophosphamide
Procedure: T-cell Infusion
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous CD19 Specific T-cell Infusion in Patients With B-cell Chronic Lymphocytic Leukemia (B-CLL)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of CD19-specific T cells [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined as the highest dose for which the posterior probability of toxicity is closest to 25%. Dose limiting toxicity (DLT) defined as new adverse events of grade 3+ (CTCAE version 4) involving cardiopulmonary, gastrointestinal, hepatic (excluding albumin), neurological, or renal parameters occurring with 6 weeks of infusion that are probably or definitely related to T-cell product. The maximum acceptable toxicity rate is 25%.


Estimated Enrollment: 30
Study Start Date: June 2013
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T-Cell Infusion + Chemotherapy
Peripheral blood mononuclear cells (PBMC) collected via venipuncture or steady state leukapheresis after enrollment. Clinically successful T-cell production defined as amount of T-cells required for dose level for which the patient is enrolled. Fludarabine 25 mg/m2 by vein on Days -5 to Day -3. Cyclophosphamide 250 mg/kg by vein on Days -5 to -3. On Day 0, 25% of genetically modified cells will be infused. On Day +1, remaining T-cell dose infused.
Procedure: Leukapheresis
Blood drawn through a needle in a vein in one arm, then passed though a machine to collect white blood cells, and then remaining blood returned back to patient through a needle in a vein in other arm. Procedure will take about 3 hours to complete.
Drug: Fludarabine
25 mg/m2 by vein on Days -5 to Day -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Cyclophosphamide
250 mg/kg by vein on Days -5 to -3.
Other Names:
  • Cytoxan
  • Neosar
Procedure: T-cell Infusion
25% of genetically modified cells infused by vein on Day 0. On Day +1, remaining T-cell dose infused.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with a history of B-CLL, who have received at least 2 lines of standard chemoimmunotherapy and have persistent disease.
  2. Confirmed history of CD19 positivity by flow cytometry.
  3. At least 8 weeks from last cytotoxic chemotherapy. Patients may continue ibrutinib or lenalidomide.
  4. Karnofsky Performance Scale > 60%.
  5. Absolute lymphocyte count >100/uL.
  6. Adequate hepatic function, as defined by SGPT <3 x upper limit of normal; serum bilirubin and alkaline phosphatase <2 x upper limit of normal, or considered not clinically significant by the study doctor or designee.
  7. Able to provide written informed consent.
  8. 18-80 years of age.
  9. Patient or patient's legal representative, parent(s) or guardian able to provide written informed consent for the long-term follow-up gene therapy study.

Exclusion Criteria:

  1. Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females.
  2. Patients with known allergy to bovine or murine products.
  3. Positive serology for HIV.
  4. Presence of autoimmune phenomenon (AIHA, ITP) requiring steroid therapy.
  5. Presence of Grade 3 or greater toxicity from the previous treatment.
  6. Concomitant use of other investigational agents (ibrutinib or lenalidomide are allowed).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01653717

Contacts
Contact: Chitra M. Hosing, MD 713-792-8750

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chitra M. Hosing, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01653717     History of Changes
Other Study ID Numbers: 2011-1169, NCI-2013-01084
Study First Received: July 27, 2012
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Leukemia
B-cell Chronic Lymphocytic Leukemia
B-CLL
CD19 positivity
CD19-specific T cells
T-Cell Infusion
Gene Transfer
Leukapheresis
Fludarabine
Fludarabine Phosphate
Fludara
Cyclophosphamide
Cytoxan
Neosar

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms
Neoplasms by Histologic Type
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014