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

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:

MedlinePlus related topics: Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate

U.S. FDA Resources

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:	August 2013
Estimated Primary Completion Date:	August 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.

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:

At the time of consent: Patients with a history of B-CLL, who have progressed after 2 lines of standard chemoimmunotherapy.
Confirmed history of CD19 positivity by flow cytometry.
At least 8 weeks from last cytotoxic chemotherapy
Karnofsky Performance Scale > 60%.
Absolute lymphocyte count >100/uL.
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.
Able to provide written informed consent.
18-80 years of age.
Within 60 days of T-cell infusion: Cardiac function: left ventricular ejection fraction >/= 50%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease. Adequate pulmonary function with FEV1, FVC, and corrected DLCO of > 50%.

Exclusion Criteria:

Richter's transformation.
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.
Patients with known allergy to bovine or murine products.
Positive serology for HIV.
Presence of autoimmune phenomenon (AIHA, ITP) requiring steroid therapy.
Presence of Grade 3 or greater toxicity from the previous treatment.
Concomitant use of other investigational agents.
Refusal to participate in the long-term follow-up study (2006-0676).

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	Not yet 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:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01653717 History of Changes
Other Study ID Numbers:	2011-1169
Study First Received:	July 27, 2012
Last Updated:	May 16, 2013
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 May 19, 2013