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

January 9, 2019 updated by: Memorial Sloan Kettering Cancer Center

A Phase I Trial of 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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: consolidative therapy with autologous T cells genetically
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
Patients will first receive a single infusion of therapy conditioning with cyclophosphamide.
Biological: modified T cells
followed by consolidative therapy with the modified T cells in 3 planned cohorts.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
toxicity
Time Frame: 2 years
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)
Time Frame: 2 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
disease response
Time Frame: 2 years
The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment will be repeated to document the degree of maximal response.
2 years
change in cellular and cytokine tumor microenvironment
Time Frame: 2 years
Cellular tumor microenvironment analysis: The presence of regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), as well as the presence of immune effector cells including dendritic cells, NK cells, and effector T cells will be assessed by fluorescence-activated cell sorting (FACS).
2 years
the impact of infused modified T cells
Time Frame: 2 years
Persistence of gene-modified T cells is defined by the presence of any percentage of detectable cells. The percentage of gene-modified T cells/ total T cells will be recorded for all patients treated at each dose level. In addition, gene-modified T cells will be measured daily for two days, weekly for eight weeks and monthly for six months (by FACS and RT-PCR).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 22, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 7, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 7, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 12, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 11, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 11-048

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