Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab

NCT01416974 | Completed Phase 1

• 1 other identifier: 11-048
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this Phase I study is to test the safety and effect of specially prepared cells collected from the patients called "modified T cells." We want to find a safe dose of modified T cells for patients who have disease remaining after initial chemotherapy. We also want to find out what effects these T cells have on you and your leukemia.

Conditions

Leukemia

Keywords

19-28Z RETROVIRUS; CYCLOPHOSPHAMIDE (CYTOXAN); autologous T cells; Leukapheresis; 11-048

Outcome Measures

Primary Outcomes (2)

• toxicity

  Criteria for toxicity: Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0

  2 years

• maximum tolerated dose (MTD)

  If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT) then the next dose level will be studied in another cohort of 3 patients

  2 years

Secondary Outcomes (3)

• disease response

  2 years

• change in cellular and cytokine tumor microenvironment

  2 years

• the impact of infused modified T cells

  2 years

Study Arms (1)

consolidative therapy with autologous T cells genetically

EXPERIMENTAL

A phase I trial of consolidation therapy with autologous T cells genetically targeted to the B cell specific antigen CD19 for patients with chronic lymphocytic leukemia following upfront chemotherapy with pentostatin, cyclophosphamide and rituximab.

Drug: cyclophosphamide; Biological: modified T cells

Interventions

cyclophosphamide DRUG

Patients will first receive a single infusion of therapy conditioning with cyclophosphamide.

consolidative therapy with autologous T cells genetically

modified T cells BIOLOGICAL

followed by consolidative therapy with the modified T cells in 3 planned cohorts.

consolidative therapy with autologous T cells genetically

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CLL patients with evidence of residual disease, who have achieved PR, nPR or CR with detectable MRD following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab.
• The presence of MRD will be assessed by the flow cytometry and polymerasechain reaction at the MSKCC Diagnostic Molecular Pathology Laboratory.
• Age ≥ 18 years of age.
• Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.
• Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.

You may not qualify if:

• Karnofsky performance status \<70.
• Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
• Impaired cardiac function (LVEF \<40%) as assessed by ECHO or MUGA scan.
• Patients previously treated with allogeneic bone marrow or stem cell transplantation are ineligible.
• Patients who are immediate candidates for allogeneic bone marrow or stem cell transplantation. Patients who refuse this option remain eligible and need to be documented as such in patient medical record.
• CLL patients with transformed disease (Richter's transformation) are ineligible for enrollment on this study.
• Patients with following cardiac conditions will be excluded:
• New York Heart Association (NYHA) stage III or IV congestive heart failure
• Myocardial infarction ≤6 months prior to enrollment
• History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
• History of severe non-ischemic cardiomyopathy with EF ≤20%
• Patients with HIV and active hepatitis B or hepatitis C infection are ineligible.
• Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation, with the exception of squamous and basal cell carcinoma of skin.
• STEP 2 REGISTRATION (Treatment):
• The following additional criteria must be met in order for a patient to be eligible to receive the modified T cell infusion. These labs are to be obtained within 2 weeks of T cell infusion.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jae Park, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2011
• First Posted: August 15, 2011
• Study Start: August 22, 2011
• Primary Completion: January 7, 2019
• Study Completion: January 7, 2019
• Last Updated: January 11, 2019

Record last verified: 2019-01

Locations

US (1)