LeukemiaPhase 1/2NCT00466531
Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
A Phase 1/2 study testing therapeutic autologous lymphocytes and cyclophosphamide in people with Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- therapeutic autologous lymphocytes and cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2007to Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have the following CD19+ B cell leukemia or lymphoma either with relapsed or chemotherapy-refractory disease or with evidence of residual disease following therapy.
- In all cases, patient's disease must be confirmed at MSKCC.
- CLL: Patients must have a diagnosis of CLL as evidenced by flow cytometry, bone marrow histology, and/or cytogenetics.
- Other low grade B-cell neoplasms are eligible for study, such as small lymphocytic lymphoma (SLL), follicular lymphoma, Waldenstrom's macroglobulinemia, hairy cell leukemia, marginal zone lymphomas, and mantle cell lymphomas.
- 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, granulocytes ≥1,000/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support
- Adequate cardiac function (LVEF ≥40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment.
- Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.
- Life expectancy of > 3 months.
Who cannot join
- Karnofsky performance status <70.
- CLL patients with active 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
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- History of severe non-ischemic cardiomyopathy with EF ≤20%
- Patients with HIV, 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase I/IIa Trial For The Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
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 is a two-stage protocol, consisting of a single-institution phase I safety study and multi-institution phase IIa extension study.
Read the detailed description
OBJECTIVES:
Phase 1: The primary objective is to assess the safety of autologous T cells genetically modified to express chimeric antigen receptor (CAR) targeting CD19 antigen (19-28z) with or without conditioning chemotherapy.
- Phase IIa: The primary objective is to compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 (19-28z) and 4-1BB (CART-19:CD3z-4-1BB) in the CAR construct.
To compare the in vivo survival of genetically modified 19-28z CAR+ T cells after T cell infusion alone or in combination with conditioning chemotherapy.
- To compare the gene transfer/expression efficiency of the two viral vectors (retrovirus vs. lentivirus).
- To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T cells linked to the CD28 (19-28z) and 4-1BB signaling domains (CART-19:CD3z-4-1BB).
OUTLINE:
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy. In Step 1, a cohort of patients will receive the lowest planned dose of 19-28z+ modified T cells. In Step 2, a cohort of patients will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of patients in the cohort (Step 2) experience unanticipated dose-limiting toxicity. In Step 3, a cohort of patients will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of patients in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be be expanded to include up to 15 patients. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) patients will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells. However, to maximize safety for WM patients, they will be treated at the lower dose of modified T cells (1x106 19-28z+ T cells/kg). If no toxicity is observed in the initial cohort, the dose may be increased in a standard 3-step dose-escalation scheme as described above.
In the Phase IIa extension part of the trial, 12 patients from MSKCC will be enrolled, and will be treated with co-infusion of 19-28z and CART-19:CD3z-4-1BB+ modified T cells mixed at 1:1 ratio at the MTD of T cells determined from the phase I trial.
- Conditions
- Leukemia
- Being tested
- therapeutic autologous lymphocytes, cyclophosphamide
- Keywords
- refractory chronic lymphocytic leukemia, 06-138
- Medical subject headings
- Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic autologous lymphocytesBiological
cyclophosphamideDrug
| Study group | Role | What they receive |
|---|---|---|
| Patients with CLL or indolent B-cell lymphoma | Experimental | The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy.Step 1, a cohort of pts will receive the lowest planned dose of 19-28z+ modified T cells. Step 2, a cohort of pts will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of pts in the cohort experience unanticipated dose-limiting toxicity,Step 3, a cohort of pts will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of pts in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be expanded to include up to 15 pts. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) pts will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells. Receives: Biological: therapeutic autologous lymphocytes; Drug: cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (phase I)
Measured: 1 year
efficacy of the two CD19-targeted T cell methods (phase II)
Measured: 1 year
Secondary outcomes (2)
Antileukemic effect
Measured: 1 year
Comparison of in vivo survival of patients receiving genetically modified anti-CD19 T cells after T-cell infusion with vs without lymphodepleting therapy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2007 (estimated)
- Study start21 Mar 2007
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jae Park, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00466531
- Sponsor's protocol ID
- 06-138
- Other IDs
- MSKCC-06138
- Status last verified
- Apr 2026
- First submitted
- 25 Apr 2007
- Last updated
- 16 Apr 2026
- Results posted
- No
Publications
Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011 Nov 3;118(18):4817-28. doi: 10.1182/blood-2011-04-348540. Epub 2011 Aug 17.
PubMed 21849486Krawczyk M, Druzynska M, Bednarska E, Winiarska M. The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies. Biochim Biophys Acta Rev Cancer. 2026 Feb;1881(1):189519. doi: 10.1016/j.bbcan.2025.189519. Epub 2025 Dec 20.
PubMed 41429239Geyer MB, Riviere I, Senechal B, Wang X, Wang Y, Purdon TJ, Hsu M, Devlin SM, Palomba ML, Halton E, Bernal Y, van Leeuwen DG, Sadelain M, Park JH, Brentjens RJ. Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL. JCI Insight. 2019 Apr 2;5(9):e122627. doi: 10.1172/jci.insight.122627.
PubMed 30938714
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa Trial For The Treatment of Relapsed or Chemotherapy Refractory Chronic Lymphocytic Leukemia or Indolent B Cell Lymphoma Using Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
- ClinicalTrials.gov ID
- NCT00466531
- Acronym / sponsor ID
- 06-138
- Conditions
- Leukemia
- Keywords
- refractory chronic lymphocytic leukemia, 06-138
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 21 Mar 2007
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 27 Apr 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 is a two-stage protocol, consisting of a single-institution phase I safety study and multi-institution phase IIa extension study.
Detailed description
OBJECTIVES:
Phase 1: The primary objective is to assess the safety of autologous T cells genetically modified to express chimeric antigen receptor (CAR) targeting CD19 antigen (19-28z) with or without conditioning chemotherapy.
- Phase IIa: The primary objective is to compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 (19-28z) and 4-1BB (CART-19:CD3z-4-1BB) in the CAR construct.
To compare the in vivo survival of genetically modified 19-28z CAR+ T cells after T cell infusion alone or in combination with conditioning chemotherapy.
- To compare the gene transfer/expression efficiency of the two viral vectors (retrovirus vs. lentivirus).
- To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T cells linked to the CD28 (19-28z) and 4-1BB signaling domains (CART-19:CD3z-4-1BB).
OUTLINE:
The first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy. In Step 1, a cohort of patients will receive the lowest planned dose of 19-28z+ modified T cells. In Step 2, a cohort of patients will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of patients in the cohort (Step 2) experience unanticipated dose-limiting toxicity. In Step 3, a cohort of patients will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of patients in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be be expanded to include up to 15 patients. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) patients will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells. However, to maximize safety for WM patients, they will be treated at the lower dose of modified T cells (1x106 19-28z+ T cells/kg). If no toxicity is observed in the initial cohort, the dose may be increased in a standard 3-step dose-escalation scheme as described above.
In the Phase IIa extension part of the trial, 12 patients from MSKCC will be enrolled, and will be treated with co-infusion of 19-28z and CART-19:CD3z-4-1BB+ modified T cells mixed at 1:1 ratio at the MTD of T cells determined from the phase I trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with CLL or indolent B-cell lymphoma | Experimental | Biological: therapeutic autologous lymphocytes, Drug: cyclophosphamideThe first stage is a standard 3-step phase I dose escalation trial to assess the safety of 19-28z CAR expressing autologous T cells with or without prior conditioning chemotherapy.Step 1, a cohort of pts will receive the lowest planned dose of 19-28z+ modified T cells. Step 2, a cohort of pts will receive cyclophosphamide conditioning chemotherapy followed by the lowest planned dose of 19-28z+ modified T cells. If less than 33% of pts in the cohort experience unanticipated dose-limiting toxicity,Step 3, a cohort of pts will be treated with the investigator's choice conditioning chemotherapy followed by the higher dose of 19-28z+ modified T cells. If less than 33% of pts in the initial cohort (Step 3) experience unanticipated dose-limiting toxicity, the cohort in Step 3 may be expanded to include up to 15 pts. In Step 3, an additional cohort of Waldenstrom's Macroglobulinemia (WM) pts will be treated with the investigator's choice conditioning chemotherapy followed by 19-28z+ T cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have the following CD19+ B cell leukemia or lymphoma either with relapsed or chemotherapy-refractory disease or with evidence of residual disease following therapy.
- In all cases, patient's disease must be confirmed at MSKCC.
- CLL: Patients must have a diagnosis of CLL as evidenced by flow cytometry, bone marrow histology, and/or cytogenetics.
- Other low grade B-cell neoplasms are eligible for study, such as small lymphocytic lymphoma (SLL), follicular lymphoma, Waldenstrom's macroglobulinemia, hairy cell leukemia, marginal zone lymphomas, and mantle cell lymphomas.
- 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, granulocytes ≥1,000/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support
Key exclusion criteria (9 listed)
- Karnofsky performance status <70.
- CLL patients with active 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| therapeutic autologous lymphocytes | Biological | Patients with CLL or indolent B-cell lymphoma |
| cyclophosphamide | Drug | Patients with CLL or indolent B-cell lymphoma |
Primary outcome
Safety (phase I)
Time frame: 1 year
efficacy of the two CD19-targeted T cell methods (phase II)
Time frame: 1 year
2 secondary outcomes
Antileukemic effect
Time frame: 1 year
Comparison of in vivo survival of patients receiving genetically modified anti-CD19 T cells after T-cell infusion with vs without lymphodepleting therapy
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Background: PubMed 21849486Brentjens RJ, Riviere I, Park JH, Davila ML, Wang X, Stefanski J, Taylor C, Yeh R, Bartido S, Borquez-Ojeda O, Olszewska M, Bernal Y, Pegram H, Przybylowski M, Hollyman D, Usachenko Y, Pirraglia D, Hosey J, Santos E, Halton E, Maslak P, Scheinberg D, Jurcic J, Heaney M, Heller G, Frattini M, Sadelain M. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011 Nov 3;118(18):4817-28. doi: 10.1182/blood-2011-04-348540. Epub 2011 Aug 17.
- Derived from this study: PubMed 41429239Krawczyk M, Druzynska M, Bednarska E, Winiarska M. The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies. Biochim Biophys Acta Rev Cancer. 2026 Feb;1881(1):189519. doi: 10.1016/j.bbcan.2025.189519. Epub 2025 Dec 20.
- Derived from this study: PubMed 30938714Geyer MB, Riviere I, Senechal B, Wang X, Wang Y, Purdon TJ, Hsu M, Devlin SM, Palomba ML, Halton E, Bernal Y, van Leeuwen DG, Sadelain M, Park JH, Brentjens RJ. Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL. JCI Insight. 2019 Apr 2;5(9):e122627. doi: 10.1172/jci.insight.122627.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae Park, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing therapeutic autologous lymphocytes and cyclophosphamide in people with Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (phase I) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00466531, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.