Laboratory-Treated T Cells With or Without Cyclophosphamide in Treating Patients With Refractory Chronic Lymphocytic Leukemia - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00466531

Purpose

RATIONALE: Using T cells from the patient that have been treated in the laboratory may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving laboratory-treated T cells together with cyclophosphamide may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated T cells alone or together with cyclophosphamide in treating patients with refractory chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: cyclophosphamide Drug: therapeutic autologous lymphocytes	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Trial for the Treatment of Purine Analog-Refractory Chronic Lymphocytic Leukemia Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Antileukemic effect [ Designated as safety issue: No ]
Comparison of in vivo survival of patients receiving genetically modified anti-CD19 T cells after T-cell infusion with vs without lymphodepleting therapy [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	March 2007
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the in vivo safety of adoptive transfer with genetically modified autologous CD19-specific T cells (both as a single therapeutic agent and in combination with lymphodepleting therapy comprising cyclophosphamide) in patients with refractory chronic lymphocytic leukemia.

Secondary

Assess the antileukemic effect of this treatment in these patients.
Compare in vivo survival of genetically modified anti-CD19 T cells after infusion either with vs without prior lymphodepleting therapy.

OUTLINE: This is a two-part dose-escalation study of transduced T cells (part 1) and cyclophosphamide with transduced T cells (part 2).

Part 1: Patients undergo leukapheresis. On day 0, T cells are isolated from leukapheresis product and CD19-specific T cells are generated by retroviral transduction and expanded. Patients receive transduced T cells IV over 1-2 hours once between days 10-22.

Cohorts of 3-6 patients receive escalating doses of transduced T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity.

Part 2: Patients undergo leukapheresis as in part 1. T cells are isolated, transduced, and expanded as in part 1. Patients receive cyclophosphamide IV between days 10-22. Two days later, patients receive transduced T cells at the MTD determined in part 1.

Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience a dose-limiting toxicity.

After completion of study treatment, patients are followed periodically for 15 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of chronic lymphocytic leukemia (CLL) confirmed by flow cytometry, bone marrow histology, and/or cytogenetics
Purine analogue-refractory disease, defined as stable or progressive disease on purine analogue-based therapy OR relapsed disease within 6 months after completion of purine analogue-based therapy
- Evidence of persistent or relapsed disease
No transformed disease (Richter's transformation)
Not an immediate candidate for allogeneic bone marrow or stem cell transplantation
- Patients who refuse this option are eligible

PATIENT CHARACTERISTICS:

Life expectancy > 3 months
Karnofsky performance status 70-100%
Creatinine < 2.0 mg/dL
Bilirubin < 2.0 mg/dL
AST and ALT < 3 times normal
Absolute granulocyte count ≥ 1,000/mm³
Platelet count ≥ 50,000/mm³
Hemoglobin ≥ 8 g/dL
LVEF > 50% as assessed by ECHO or MUGA scan performed within 1 month of treatment
No clinically significant heart disease (i.e., NYHA class III or IV heart disease) or other serious intercurrent illnesses, active uncontrolled infections requiring antibiotics, or active bleeding
Not pregnant or nursing
Negative pregnancy test
No HIV, hepatitis B, or hepatitis C infection
No history of other active malignancies except for any of the following:
- Curatively treated cutaneous basal cell carcinoma
- Carcinoma in situ of the cervix
- Axillary-node negative breast cancer treated without chemotherapy and disease free for > 2 years
- Prostate cancer treated with surgery or radiation therapy alone and disease free for > 2 years

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior treatment with allogeneic bone marrow or stem cell transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466531

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10021
Contact: Renier Brentjens, MD, PhD 212-639-7053

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Renier Brentjens, MD, PhD	Memorial Sloan-Kettering Cancer Center
Principal Investigator:	Isabelle Riviere, PhD	Memorial Sloan-Kettering Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000540585, MSKCC-06138
Study First Received:	April 25, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00466531
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory chronic lymphocytic leukemia

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Cyclophosphamide
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009