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Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01865617
Enrollment
204
Registered
2013-05-31
Start date
2013-05-22
Completion date
2021-03-26
Last updated
2022-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

CD19-Positive Neoplastic Cells Present, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Chronic Lymphocytic Leukemia, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Acute Lymphoblastic Leukemia, Refractory Chronic Lymphocytic Leukemia, Refractory Diffuse Large B-Cell Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Non-Hodgkin Lymphoma, Refractory Small Lymphocytic Lymphoma

Brief summary

This phase I/II trial studies the side effects and best dose of laboratory treated T cells to see how well they work in treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia that have come back or have not responded to treatment. T cells that are treated in the laboratory before being given back to the patient may make the body build an immune response to kill cancer cells.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded autologous CD8 positive (+) and CD4+ CD19 chimeric antigen receptor (CAR)-T cells for patients with advanced CD19+ B cell malignancies. SECONDARY OBJECTIVES: I. To determine the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. II. To determine if adoptively transferred T cells traffic to the bone marrow and function in vivo. III. To determine if the adoptive transfer of CD19 CAR-T cells results in depletion of CD19+ B cells in vivo as a surrogate for functional activity. IV. To determine if the adoptive transfer of CD19 CAR-T cells has antitumor activity in patients with measurable tumor burden prior to T cell transfer. V. To determine if the adoptive transfer of CD19 CAR-T cells is associated with tumor lysis syndrome. OUTLINE: This is a phase I, dose-escalation study of autologous CD19 CAR T-cells followed by a phase II study. Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells intravenously (IV) over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. DOSE DENSE EXPANSION COHORT: An additional cohort will receive a second anti-CD19-CAR lentiviral vector-transduced autologous T cell infusion without additional lymphodepleting chemotherapy 10-21 days after the first infusion if adequate CD19 CAR-T cells can be produced and appropriate criteria are met. After completion of study treatment, patients are followed up for at least 15 years.

Interventions

BIOLOGICALAutologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes

Given IV

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Fred Hutchinson Cancer Center
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

INCLUSIONS FOR SCREENING AND LEUKAPHERESIS * Patients with CD19 expressing acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) * Ability to understand and provide informed consent * Not human immunodeficiency virus (HIV) infected INCLUSIONS FOR CAR-T CELL THERAPY * Patients with: * CLL who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody or who were not eligible for such therapy; patients with CLL for whom ibrutinib is now standard first line therapy, must have progressed on ibrutinib; patients with fludarabine refractory disease are eligible; patients may be treated following allogeneic hematopoietic cell transplant (HCT); for the concurrent ibrutinib cohort, patients must agree to continue on or be restarted on ibrutinib and must not have had prior intolerance to ibrutinib that would prevent this; patients managed with prior dose reductions for toxicity will continue at the reduced dose for the remainder of this study * Indolent NHL or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy or who were not eligible for such therapy; patients who have relapsed following autologous or allogeneic HCT are eligible * Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL), who have relapsed or have residual disease following treatment with curative intent; patients should have relapsed following, or not be eligible for high-dose therapy and autologous HCT; patients with chemotherapy refractory disease or marrow involvement or comorbidities precluding successful autologous HCT are eligible; patients may be treated following allogeneic HCT * Patients with CD19 expressing, relapsed or refractory ALL * Patients with one of the above diagnoses whose disease state does not qualify but who have prognostic indicators that suggest a high risk of progression of disease may be screened and undergo leukapheresis; enrollment for T cell therapy would require meeting the full disease state eligibility * Confirmation of diagnosis * Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology * Karnofsky performance status \>= 60% * All patients of childbearing potential must be willing to use a contraceptive method before, during, and for at least two months after the T cell infusion * Ability to understand and provide informed consent

Exclusion criteria

EXCLUSIONS FOR CAR-T CELL THERAPY * Patients requiring ongoing daily corticosteroid therapy at a dose of \> 15 mg of prednisone per day (or equivalent); pulsed corticosteroid use for disease control is acceptable * Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the Principal Investigator (PI) * Serum creatinine \> 2.5 mg/dL * Serum glutamic oxaloacetic transaminase (SGOT) \> 5 x upper limit of normal * Bilirubin \> 3.0 mg/dL * Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in one second (FEV1) of \< 50 % of predicted will be excluded * Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) \< 40% will be excluded * Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of \< 35% * Uncontrolled active infection

Design outcomes

Primary

MeasureTime frameDescription
Dose Limiting Toxicities30 daysOutcome will be reported as a count of participants that experienced a dose limiting toxicity on the study within 30 days post infusion.
Overall SurvivalUp to 1 yearOutcome will be reported as a count of patients who survived up to 1 year post infusion.
Progression Free SurvivalUp to 1 yearOutcome will be reported as the count of patients per arm that survived and whose disease did not progress in the 1 year timeframe post infusion.
Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell TherapyWithin 8 weeks of the study cell infusionDeath within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy will be assessed.
Objective Response Rate of Complete Response and Partial ResponseUp to 1 yearOutcome will be reported as the count of patients per arm that experienced a complete response/partial response. Complete response (CR): CR per Lugano criteria for nodal disease and minimal residual disease (MRD)-negative CR by flow cytometry for marrow disease. Partial response (PR): \> 50% reduction of the sum of the products of the perpendicular diameters of marker lesions, no progression of any existing lesions, and no new lesions.

Secondary

MeasureTime frameDescription
Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsUp to 1 yearMigration of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients with bone marrow disease involvement and count of patients with CAR-T cells detected in bone marrow at restaging.
Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsUp to day 365Duration of persistence of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients alive after 1 year and count of patients with CAR-T cells detected at 1 year.

Countries

United States

Participant flow

Pre-assignment details

204 patients were enrolled on this study but only 197 met eligibility criteria and went on to be treated on study.

Participants by arm

ArmCount
ALL (High Tumor Burden) Dose Level 1
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 1 up to 2x105 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
39
ALL (High Tumor Burden) Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
5
ALL (High Tumor Burden) Dose Level 3
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 3 up to 2x107 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
2
ALL (Low Tumor Burden) Dose Level 1
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: low Dose level: 1 up to 2x105 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
1
ALL (Low Tumor Burden) Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: ALL Tumor Burden: high Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
18
CLL Dose Level 1
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 1 up to 2x105 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
5
CLL Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
22
CLL Dose Level 3
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL Dose level: 3 up to 2x107 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
1
CLL (Ibrutinib) Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: CLL (ibrutinib) Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
20
NHL Dose Level 1
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 1 up to 2x105 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
5
NHL Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
49
NHL Dose Level 3
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 3 up to 2x107 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
10
NHL (Dose Dense) Dose Level 2
Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity. Disease subgroup: NHL Dose level: 2 up to 2x106 EGFR+ cells/kg Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes: Given IV
20
Total197

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009FG010FG011FG012
Overall StudyDeath273115111111332613
Overall StudyLost to Follow-up2000000000000
Overall StudyOther0000001000000
Overall StudyPatient proceeded to new therapy0000200000000
Overall StudyWithdrawal by Subject1000000000000

Baseline characteristics

CharacteristicTotalALL (High Tumor Burden) Dose Level 2ALL (High Tumor Burden) Dose Level 3ALL (Low Tumor Burden) Dose Level 1ALL (Low Tumor Burden) Dose Level 2CLL Dose Level 1CLL Dose Level 2ALL (High Tumor Burden) Dose Level 1CLL Dose Level 3CLL (Ibrutinib) Dose Level 2NHL Dose Level 1NHL Dose Level 2NHL Dose Level 3NHL (Dose Dense) Dose Level 2
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
39 Participants0 Participants1 Participants0 Participants3 Participants1 Participants5 Participants4 Participants0 Participants8 Participants1 Participants9 Participants2 Participants5 Participants
Age, Categorical
Between 18 and 65 years
158 Participants5 Participants1 Participants1 Participants15 Participants4 Participants17 Participants35 Participants1 Participants12 Participants4 Participants40 Participants8 Participants15 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
14 Participants1 Participants0 Participants0 Participants4 Participants0 Participants1 Participants6 Participants0 Participants0 Participants0 Participants2 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
182 Participants4 Participants2 Participants1 Participants14 Participants5 Participants20 Participants33 Participants1 Participants20 Participants5 Participants47 Participants10 Participants20 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
7 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants3 Participants0 Participants0 Participants0 Participants1 Participants0 Participants1 Participants
Race/Ethnicity, Customized
Asian
12 Participants0 Participants0 Participants1 Participants2 Participants0 Participants1 Participants4 Participants0 Participants0 Participants0 Participants1 Participants0 Participants3 Participants
Race/Ethnicity, Customized
Black or African American
4 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants0 Participants2 Participants
Race/Ethnicity, Customized
Mexican or Mexican American
4 Participants1 Participants0 Participants0 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants
Race/Ethnicity, Customized
Unknown
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race/Ethnicity, Customized
White
167 Participants4 Participants2 Participants0 Participants13 Participants4 Participants19 Participants31 Participants1 Participants19 Participants5 Participants45 Participants10 Participants14 Participants
Race/Ethnicity, Customized
White American Indian or Alaska Native
1 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Region of Enrollment
United States
197 participants5 participants2 participants1 participants18 participants5 participants22 participants39 participants1 participants20 participants5 participants49 participants10 participants20 participants
Sex: Female, Male
Female
66 Participants2 Participants2 Participants1 Participants8 Participants2 Participants7 Participants16 Participants0 Participants6 Participants2 Participants13 Participants2 Participants5 Participants
Sex: Female, Male
Male
131 Participants3 Participants0 Participants0 Participants10 Participants3 Participants15 Participants23 Participants1 Participants14 Participants3 Participants36 Participants8 Participants15 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
EG008
affected / at risk
EG009
affected / at risk
EG010
affected / at risk
EG011
affected / at risk
EG012
affected / at risk
deaths
Total, all-cause mortality
27 / 393 / 51 / 21 / 15 / 181 / 511 / 221 / 111 / 203 / 532 / 496 / 1013 / 20
other
Total, other adverse events
39 / 395 / 52 / 21 / 118 / 185 / 522 / 221 / 120 / 205 / 549 / 4910 / 1019 / 20
serious
Total, serious adverse events
39 / 395 / 52 / 20 / 114 / 185 / 522 / 221 / 120 / 205 / 549 / 497 / 1020 / 20

Outcome results

Primary

Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy

Death within 8 weeks of the study cell infusion thought to be definitely or probably related to CAR T cell therapy will be assessed.

Time frame: Within 8 weeks of the study cell infusion

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
ALL (High Tumor Burden) Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
ALL (High Tumor Burden) Dose Level 3Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy1 Participants
ALL (Low Tumor Burden) Dose Level 1Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
ALL (Low Tumor Burden) Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy1 Participants
CLL Dose Level 1Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
CLL Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy1 Participants
CLL Dose Level 3Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
CLL (Ibrutinib) Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy1 Participants
NHL Dose Level 1Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
NHL Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
NHL Dose Level 3Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
NHL (Dose Dense) Dose Level 2Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy0 Participants
Primary

Dose Limiting Toxicities

Outcome will be reported as a count of participants that experienced a dose limiting toxicity on the study within 30 days post infusion.

Time frame: 30 days

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Dose Limiting Toxicities3 Participants
ALL (High Tumor Burden) Dose Level 2Dose Limiting Toxicities1 Participants
ALL (High Tumor Burden) Dose Level 3Dose Limiting Toxicities1 Participants
ALL (Low Tumor Burden) Dose Level 1Dose Limiting Toxicities0 Participants
ALL (Low Tumor Burden) Dose Level 2Dose Limiting Toxicities2 Participants
CLL Dose Level 1Dose Limiting Toxicities0 Participants
CLL Dose Level 2Dose Limiting Toxicities4 Participants
CLL Dose Level 3Dose Limiting Toxicities0 Participants
CLL (Ibrutinib) Dose Level 2Dose Limiting Toxicities1 Participants
NHL Dose Level 1Dose Limiting Toxicities0 Participants
NHL Dose Level 2Dose Limiting Toxicities0 Participants
NHL Dose Level 3Dose Limiting Toxicities3 Participants
NHL (Dose Dense) Dose Level 2Dose Limiting Toxicities0 Participants
Primary

Objective Response Rate of Complete Response and Partial Response

Outcome will be reported as the count of patients per arm that experienced a complete response/partial response. Complete response (CR): CR per Lugano criteria for nodal disease and minimal residual disease (MRD)-negative CR by flow cytometry for marrow disease. Partial response (PR): \> 50% reduction of the sum of the products of the perpendicular diameters of marker lesions, no progression of any existing lesions, and no new lesions.

Time frame: Up to 1 year

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Objective Response Rate of Complete Response and Partial Response32 Participants
ALL (High Tumor Burden) Dose Level 2Objective Response Rate of Complete Response and Partial Response5 Participants
ALL (High Tumor Burden) Dose Level 3Objective Response Rate of Complete Response and Partial Response1 Participants
ALL (Low Tumor Burden) Dose Level 1Objective Response Rate of Complete Response and Partial Response1 Participants
ALL (Low Tumor Burden) Dose Level 2Objective Response Rate of Complete Response and Partial Response18 Participants
CLL Dose Level 1Objective Response Rate of Complete Response and Partial Response4 Participants
CLL Dose Level 2Objective Response Rate of Complete Response and Partial Response16 Participants
CLL Dose Level 3Objective Response Rate of Complete Response and Partial Response1 Participants
CLL (Ibrutinib) Dose Level 2Objective Response Rate of Complete Response and Partial Response12 Participants
NHL Dose Level 1Objective Response Rate of Complete Response and Partial Response2 Participants
NHL Dose Level 2Objective Response Rate of Complete Response and Partial Response28 Participants
NHL Dose Level 3Objective Response Rate of Complete Response and Partial Response4 Participants
NHL (Dose Dense) Dose Level 2Objective Response Rate of Complete Response and Partial Response10 Participants
Primary

Overall Survival

Outcome will be reported as a count of patients who survived up to 1 year post infusion.

Time frame: Up to 1 year

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Overall Survival12 Participants
ALL (High Tumor Burden) Dose Level 2Overall Survival2 Participants
ALL (High Tumor Burden) Dose Level 3Overall Survival1 Participants
ALL (Low Tumor Burden) Dose Level 1Overall Survival0 Participants
ALL (Low Tumor Burden) Dose Level 2Overall Survival13 Participants
CLL Dose Level 1Overall Survival4 Participants
CLL Dose Level 2Overall Survival13 Participants
CLL Dose Level 3Overall Survival0 Participants
CLL (Ibrutinib) Dose Level 2Overall Survival9 Participants
NHL Dose Level 1Overall Survival2 Participants
NHL Dose Level 2Overall Survival20 Participants
NHL Dose Level 3Overall Survival4 Participants
NHL (Dose Dense) Dose Level 2Overall Survival7 Participants
Primary

Progression Free Survival

Outcome will be reported as the count of patients per arm that survived and whose disease did not progress in the 1 year timeframe post infusion.

Time frame: Up to 1 year

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Progression Free Survival2 Participants
ALL (High Tumor Burden) Dose Level 2Progression Free Survival0 Participants
ALL (High Tumor Burden) Dose Level 3Progression Free Survival0 Participants
ALL (Low Tumor Burden) Dose Level 1Progression Free Survival0 Participants
ALL (Low Tumor Burden) Dose Level 2Progression Free Survival1 Participants
CLL Dose Level 1Progression Free Survival3 Participants
CLL Dose Level 2Progression Free Survival4 Participants
CLL Dose Level 3Progression Free Survival0 Participants
CLL (Ibrutinib) Dose Level 2Progression Free Survival2 Participants
NHL Dose Level 1Progression Free Survival0 Participants
NHL Dose Level 2Progression Free Survival4 Participants
NHL Dose Level 3Progression Free Survival1 Participants
NHL (Dose Dense) Dose Level 2Progression Free Survival2 Participants
Secondary

Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells

Duration of persistence of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients alive after 1 year and count of patients with CAR-T cells detected at 1 year.

Time frame: Up to day 365

Population: Cohorts for this outcome are combined into disease type. The first row is a count of participants that were alive at the 1 year post infusion point within these cohorts. The second row is a count of participants who had CAR-T cells present at the 1 year follow up. This count has a lower number analyzed because it is out of the participants who had available CAR-T data at the 1 year followup timepoint.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients alive 1 year after CAR-T cell infusion33 Participants
ALL (High Tumor Burden) Dose Level 1Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected at 1 year3 Participants
ALL (High Tumor Burden) Dose Level 2Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients alive 1 year after CAR-T cell infusion46 Participants
ALL (High Tumor Burden) Dose Level 2Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected at 1 year14 Participants
ALL (High Tumor Burden) Dose Level 3Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients alive 1 year after CAR-T cell infusion23 Participants
ALL (High Tumor Burden) Dose Level 3Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected at 1 year13 Participants
Secondary

Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells

Migration of adoptively transferred CD19 chimeric antigen receptor (CAR)-T cells. Outcome will be reported for each of the 3 cohorts on the study. Outcome data is both count of patients with bone marrow disease involvement and count of patients with CAR-T cells detected in bone marrow at restaging.

Time frame: Up to 1 year

Population: This outcome is split into arms by disease type. The first row is a count of participants out of those treated that had bone marrow disease involvement. The second row reports the count of participants with CAR-T cells detected in bone marrow at restaging. The total number analyzed for the count of participants with CAR-T cells detected in bone marrow at restaging is lower than the overall number analyzed because it is those who had available bone marrow data at the time of restaging.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
ALL (High Tumor Burden) Dose Level 1Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with bone marrow disease involvement62 Participants
ALL (High Tumor Burden) Dose Level 1Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected in bone marrow at restaging49 Participants
ALL (High Tumor Burden) Dose Level 2Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with bone marrow disease involvement24 Participants
ALL (High Tumor Burden) Dose Level 2Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected in bone marrow at restaging15 Participants
ALL (High Tumor Burden) Dose Level 3Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with bone marrow disease involvement47 Participants
ALL (High Tumor Burden) Dose Level 3Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T CellsCount of patients with CAR-T cells detected in bone marrow at restaging37 Participants

Source: ClinicalTrials.gov · Data processed: Jul 3, 2026