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

Sponsor
Fred Hutchinson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01865617
Collaborator
National Cancer Institute (NCI) (NIH)
204
1
13
94.1
2.2

Study Details

Study Description

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:
  1. 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:
  1. To determine the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.

  2. To determine if adoptively transferred T cells traffic to the bone marrow and function in vivo.

  3. 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.

  4. 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.

  5. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
204 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 22, 2013
Actual Primary Completion Date :
Mar 26, 2021
Actual Study Completion Date :
Mar 26, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Experimental: 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

Biological: Autologous Anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T Lymphocytes
Given IV

Outcome Measures

Primary Outcome Measures

  1. Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy [Within 8 weeks of the study cell infusion]

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

  2. Dose Limiting Toxicities [30 days]

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

  3. Objective Response Rate of Complete Response and Partial Response [Up to 1 year]

    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.

  4. Overall Survival [Up to 1 year]

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

  5. Progression Free Survival [Up to 1 year]

    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.

Secondary Outcome Measures

  1. Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells [Up to day 365]

    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.

  2. Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells [Up to 1 year]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Fred Hutch/University of Washington Cancer Consortium Seattle Washington United States 98109

Sponsors and Collaborators

  • Fred Hutchinson Cancer Center
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jordan Gauthier, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Alexandre Hirayama, Research Associate, Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT01865617
Other Study ID Numbers:
  • 2639.00
  • NCI-2013-00073
  • 2639
  • RG9213011
  • P50CA107399
  • R01CA136551
First Posted:
May 31, 2013
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 204 patients were enrolled on this study but only 197 met eligibility criteria and went on to be treated on study.
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Period Title: Overall Study
STARTED 39 5 2 1 18 5 22 1 20 5 49 10 20
COMPLETED 9 2 1 0 11 4 10 0 9 2 17 4 7
NOT COMPLETED 30 3 1 1 7 1 12 1 11 3 32 6 13

Baseline Characteristics

Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2 Total
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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 Total of all reporting groups
Overall Participants 39 5 2 1 18 5 22 1 20 5 49 10 20 197
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
35
89.7%
5
100%
1
50%
1
100%
15
83.3%
4
80%
17
77.3%
1
100%
12
60%
4
80%
40
81.6%
8
80%
15
75%
158
80.2%
>=65 years
4
10.3%
0
0%
1
50%
0
0%
3
16.7%
1
20%
5
22.7%
0
0%
8
40%
1
20%
9
18.4%
2
20%
5
25%
39
19.8%
Sex: Female, Male (Count of Participants)
Female
16
41%
2
40%
2
100%
1
100%
8
44.4%
2
40%
7
31.8%
0
0%
6
30%
2
40%
13
26.5%
2
20%
5
25%
66
33.5%
Male
23
59%
3
60%
0
0%
0
0%
10
55.6%
3
60%
15
68.2%
1
100%
14
70%
3
60%
36
73.5%
8
80%
15
75%
131
66.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
6
15.4%
1
20%
0
0%
0
0%
4
22.2%
0
0%
1
4.5%
0
0%
0
0%
0
0%
2
4.1%
0
0%
0
0%
14
7.1%
Not Hispanic or Latino
33
84.6%
4
80%
2
100%
1
100%
14
77.8%
5
100%
20
90.9%
1
100%
20
100%
5
100%
47
95.9%
10
100%
20
100%
182
92.4%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
4.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
0.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native
3
7.7%
0
0%
0
0%
0
0%
1
5.6%
0
0%
1
4.5%
0
0%
0
0%
0
0%
1
2%
0
0%
1
5%
7
3.6%
Asian
4
10.3%
0
0%
0
0%
1
100%
2
11.1%
0
0%
1
4.5%
0
0%
0
0%
0
0%
1
2%
0
0%
3
15%
12
6.1%
Black or African American
1
2.6%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2%
0
0%
2
10%
4
2%
White
31
79.5%
4
80%
2
100%
0
0%
13
72.2%
4
80%
19
86.4%
1
100%
19
95%
5
100%
45
91.8%
10
100%
14
70%
167
84.8%
Mexican or Mexican American
0
0%
1
20%
0
0%
0
0%
2
11.1%
0
0%
0
0%
0
0%
0
0%
0
0%
1
2%
0
0%
0
0%
4
2%
White American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
1
20%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
0.5%
Unknown
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
4.5%
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
1
0.5%
Region of Enrollment (participants) [Number]
United States
39
100%
5
100%
2
100%
1
100%
18
100%
5
100%
22
100%
1
100%
20
100%
5
100%
49
100%
10
100%
20
100%
197
100%

Outcome Measures

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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Measure Participants 39 5 2 1 18 5 22 1 20 5 49 10 20
Count of Participants [Participants]
0
0%
0
0%
1
50%
0
0%
1
5.6%
0
0%
1
4.5%
0
0%
1
5%
0
0%
0
0%
0
0%
0
0%
2. Primary Outcome
Title Dose Limiting Toxicities
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Measure Participants 39 5 2 1 18 5 22 1 20 5 49 10 20
Count of Participants [Participants]
3
7.7%
1
20%
1
50%
0
0%
2
11.1%
0
0%
4
18.2%
0
0%
1
5%
0
0%
0
0%
3
30%
0
0%
3. Primary Outcome
Title Objective Response Rate of Complete Response and Partial Response
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Measure Participants 39 5 2 1 18 5 22 1 20 5 49 10 20
Count of Participants [Participants]
32
82.1%
5
100%
1
50%
1
100%
18
100%
4
80%
16
72.7%
1
100%
12
60%
2
40%
28
57.1%
4
40%
10
50%
4. Primary Outcome
Title Overall Survival
Description Outcome will be reported as a count of patients who survived up to 1 year post infusion.
Time Frame Up to 1 year

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Measure Participants 39 5 2 1 18 5 22 1 20 5 49 10 20
Count of Participants [Participants]
12
30.8%
2
40%
1
50%
0
0%
13
72.2%
4
80%
13
59.1%
0
0%
9
45%
2
40%
20
40.8%
4
40%
7
35%
5. Primary Outcome
Title Progression Free Survival
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
Measure Participants 39 5 2 1 18 5 22 1 20 5 49 10 20
Count of Participants [Participants]
2
5.1%
0
0%
0
0%
0
0%
1
5.6%
3
60%
4
18.2%
0
0%
2
10%
0
0%
4
8.2%
1
10%
2
10%
6. Secondary Outcome
Title Duration of Persistence of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Acute Lymphocytic Leukemia Cohort Non-Hodgkin Lymphoma Cohort Chronic Lymphocytic Leukemia Cohort
Arm/Group Description Cohort containing all ALL subtypes and treatment dose levels. Cohort containing all NHL subtypes and treatment dose levels. Cohort containing all CLL subtypes and treatment dose levels.
Measure Participants 65 84 48
Count of patients alive 1 year after CAR-T cell infusion
33
84.6%
46
920%
23
1150%
Count of patients with CAR-T cells detected at 1 year
3
7.7%
14
280%
13
650%
7. Secondary Outcome
Title Migration of Adoptively Transferred CD19 Chimeric Antigen Receptor (CAR)-T Cells
Description 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

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Acute Lymphocytic Leukemia Cohort Non-Hodgkin Lymphoma Cohort Chronic Lymphocytic Leukemia Cohort
Arm/Group Description Cohort containing all ALL subtypes and treatment dose levels. Cohort containing all NHL subtypes and treatment dose levels. Cohort containing all CLL subtypes and treatment dose levels.
Measure Participants 65 84 48
Count of patients with bone marrow disease involvement
62
159%
24
480%
47
2350%
Count of patients with CAR-T cells detected in bone marrow at restaging
49
125.6%
15
300%
37
1850%

Adverse Events

Time Frame Adverse events will be assessed up to 1 year for each patient following their infusion.
Adverse Event Reporting Description Adverse Events will be extracted from the patient record and assessed by the Principle Investigator for relation to treatment. AEs will beb graded in severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v4.03).
Arm/Group Title ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Arm/Group Description 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 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 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 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 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 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 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 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 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 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 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 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 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
All Cause Mortality
ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 27/39 (69.2%) 3/5 (60%) 1/2 (50%) 1/1 (100%) 5/18 (27.8%) 1/5 (20%) 11/22 (50%) 1/1 (100%) 11/20 (55%) 3/5 (60%) 32/49 (65.3%) 6/10 (60%) 13/20 (65%)
Serious Adverse Events
ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 39/39 (100%) 5/5 (100%) 2/2 (100%) 0/1 (0%) 14/18 (77.8%) 5/5 (100%) 22/22 (100%) 1/1 (100%) 20/20 (100%) 5/5 (100%) 49/49 (100%) 7/10 (70%) 20/20 (100%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Febrile neutropenia 30/39 (76.9%) 42 5/5 (100%) 5 2/2 (100%) 2 0/1 (0%) 0 10/18 (55.6%) 11 4/5 (80%) 5 21/22 (95.5%) 26 1/1 (100%) 1 10/20 (50%) 10 3/5 (60%) 3 27/49 (55.1%) 34 7/10 (70%) 10 12/20 (60%) 13
Lymph node pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Cardiac disorders
Atrial fibrillation 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 1/20 (5%) 1
Cardiac arrest 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Heart failure 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Left ventricular systolic dysfunction 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Pericardial tamponade 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Sick sinus syndrome 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Sinus bradycardia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Sinus tachycardia 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 0/20 (0%) 0
Supraventricular tachycardia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Gastrointestinal disorders
Abdominal pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Anal fistula 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Colitis 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Gastric hemorrhage 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Nausea 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Pancreatitis 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
General disorders
Fever 2/39 (5.1%) 2 3/5 (60%) 3 1/2 (50%) 1 0/1 (0%) 0 2/18 (11.1%) 2 0/5 (0%) 0 4/22 (18.2%) 4 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 1/49 (2%) 1 3/10 (30%) 3 0/20 (0%) 0
General disorders and administration site conditions - Other, specify 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 1/20 (5%) 1
Multi-organ failure 1/39 (2.6%) 1 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Sudden death NOS 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hepatobiliary disorders
Hepatic failure 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 0/20 (0%) 0
Immune system disorders
Cytokine release syndrome 10/39 (25.6%) 10 5/5 (100%) 5 2/2 (100%) 2 0/1 (0%) 0 4/18 (22.2%) 4 1/5 (20%) 1 8/22 (36.4%) 8 1/1 (100%) 1 0/20 (0%) 0 1/5 (20%) 1 2/49 (4.1%) 2 5/10 (50%) 5 2/20 (10%) 2
Infections and infestations
Anorectal infection 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Appendicitis 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Bone infection 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Catheter related infection 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Infections and infestations - Other, specify 3/39 (7.7%) 3 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 2/22 (9.1%) 8 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 1/20 (5%) 1
Lung infection 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 1/5 (20%) 1 2/22 (9.1%) 2 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Sepsis 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Sinusitis 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Investigations
White blood cell decreased 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Metabolism and nutrition disorders
Tumor lysis syndrome 1/39 (2.6%) 1 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Musculoskeletal and connective tissue disorders
Arthritis 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Muscle weakness lower limb 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Nervous system disorders
Central nervous system necrosis 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Cognitive disturbance 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Depressed level of consciousness 0/39 (0%) 0 3/5 (60%) 3 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Dysarthria 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Dysphasia 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Edema cerebral 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Encephalopathy 1/39 (2.6%) 1 3/5 (60%) 3 1/2 (50%) 1 0/1 (0%) 0 2/18 (11.1%) 2 0/5 (0%) 0 3/22 (13.6%) 3 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 3/49 (6.1%) 3 2/10 (20%) 2 2/20 (10%) 2
Nervous system disorders - Other, specify 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 2 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Seizure 0/39 (0%) 0 3/5 (60%) 3 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Somnolence 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Stroke 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Psychiatric disorders
Delirium 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Depression 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Suicide attempt 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Renal and urinary disorders
Acute kidney injury 1/39 (2.6%) 1 1/5 (20%) 1 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Renal and urinary disorders - Other, specify 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Dyspnea 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hiccups 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hypoxia 1/39 (2.6%) 1 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Laryngeal edema 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Pleural effusion 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 1/49 (2%) 1 0/10 (0%) 0 1/20 (5%) 2
Pulmonary edema 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 2/22 (9.1%) 2 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Respiratory failure 1/39 (2.6%) 1 2/5 (40%) 2 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 2/10 (20%) 2 0/20 (0%) 0
Vascular disorders
Capillary leak syndrome 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hypotension 9/39 (23.1%) 9 5/5 (100%) 5 1/2 (50%) 1 0/1 (0%) 0 3/18 (16.7%) 3 0/5 (0%) 0 3/22 (13.6%) 3 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 6/49 (12.2%) 6 5/10 (50%) 5 1/20 (5%) 1
Other (Not Including Serious) Adverse Events
ALL (High Tumor Burden) Dose Level 1 ALL (High Tumor Burden) Dose Level 2 ALL (High Tumor Burden) Dose Level 3 ALL (Low Tumor Burden) Dose Level 1 ALL (Low Tumor Burden) Dose Level 2 CLL Dose Level 1 CLL Dose Level 2 CLL Dose Level 3 CLL (Ibrutinib) Dose Level 2 NHL Dose Level 1 NHL Dose Level 2 NHL Dose Level 3 NHL (Dose Dense) Dose Level 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 39/39 (100%) 5/5 (100%) 2/2 (100%) 1/1 (100%) 18/18 (100%) 5/5 (100%) 22/22 (100%) 1/1 (100%) 20/20 (100%) 5/5 (100%) 49/49 (100%) 10/10 (100%) 19/20 (95%)
Blood and lymphatic system disorders
Anemia 33/39 (84.6%) 44 4/5 (80%) 4 1/2 (50%) 1 1/1 (100%) 2 12/18 (66.7%) 15 3/5 (60%) 6 19/22 (86.4%) 27 1/1 (100%) 1 16/20 (80%) 19 4/5 (80%) 6 32/49 (65.3%) 46 6/10 (60%) 7 14/20 (70%) 20
Blood and lymphatic system disorders - Other, specify 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 2/18 (11.1%) 2 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Disseminated intravascular coagulation 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Febrile neutropenia 3/39 (7.7%) 3 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 4/20 (20%) 4 0/5 (0%) 0 3/49 (6.1%) 3 0/10 (0%) 0 0/20 (0%) 0
Leukocytosis 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Cardiac disorders
Atrial fibrillation 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Sinus bradycardia 1/39 (2.6%) 1 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Sinus tachycardia 5/39 (12.8%) 6 4/5 (80%) 4 0/2 (0%) 0 0/1 (0%) 0 3/18 (16.7%) 3 1/5 (20%) 1 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 1/5 (20%) 2 5/49 (10.2%) 5 1/10 (10%) 1 0/20 (0%) 0
Ear and labyrinth disorders
Ear pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Gastrointestinal disorders
Abdominal pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 4/49 (8.2%) 6 1/10 (10%) 1 1/20 (5%) 1
Diarrhea 2/39 (5.1%) 2 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 1/5 (20%) 1 1/22 (4.5%) 1 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 1/49 (2%) 1 3/10 (30%) 3 0/20 (0%) 0
Hemorrhoidal hemorrhage 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Lower gastrointestinal hemorrhage 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Nausea 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 3/18 (16.7%) 4 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Oral pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Rectal pain 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Vomiting 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
General disorders
Chills 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Edema limbs 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 2 0/10 (0%) 0 2/20 (10%) 2
Fatigue 2/39 (5.1%) 2 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 2/49 (4.1%) 2 1/10 (10%) 1 0/20 (0%) 0
Fever 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 1/22 (4.5%) 1 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 2/20 (10%) 2
General disorders and administration site conditions - Other, specify 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Localized edema 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Non-cardiac chest pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Immune system disorders
Cytokine release syndrome 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Infections and infestations
Anorectal infection 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Catheter related infection 3/39 (7.7%) 3 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Infections and infestations - Other, specify 3/39 (7.7%) 3 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 2 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 1/20 (5%) 2
Lung infection 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Pancreas infection 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Sinusitis 1/39 (2.6%) 1 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 2/22 (9.1%) 2 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Skin infection 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Upper respiratory infection 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Urinary tract infection 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Injury, poisoning and procedural complications
Vascular access complication 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 1/20 (5%) 1
Investigations
Activated partial thromboplastin time prolonged 8/39 (20.5%) 8 3/5 (60%) 3 1/2 (50%) 1 0/1 (0%) 0 1/18 (5.6%) 1 2/5 (40%) 2 2/22 (9.1%) 2 0/1 (0%) 0 1/20 (5%) 1 1/5 (20%) 1 2/49 (4.1%) 2 4/10 (40%) 4 2/20 (10%) 2
Alanine aminotransferase increased 4/39 (10.3%) 4 2/5 (40%) 2 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 2/5 (40%) 2 2/22 (9.1%) 2 0/1 (0%) 0 2/20 (10%) 2 1/5 (20%) 1 1/49 (2%) 1 1/10 (10%) 1 1/20 (5%) 1
Alkaline phosphatase increased 2/39 (5.1%) 3 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 2/49 (4.1%) 2 0/10 (0%) 0 0/20 (0%) 0
Aspartate aminotransferase increased 4/39 (10.3%) 4 3/5 (60%) 3 1/2 (50%) 1 0/1 (0%) 0 1/18 (5.6%) 1 2/5 (40%) 2 5/22 (22.7%) 5 0/1 (0%) 0 2/20 (10%) 2 0/5 (0%) 0 1/49 (2%) 1 1/10 (10%) 1 0/20 (0%) 0
Blood bilirubin increased 1/39 (2.6%) 1 1/5 (20%) 1 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 2/5 (40%) 2 1/22 (4.5%) 1 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 2/49 (4.1%) 3 1/10 (10%) 1 2/20 (10%) 2
Cardiac troponin I increased 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 2/10 (20%) 2 0/20 (0%) 0
CPK increased 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Creatinine increased 0/39 (0%) 0 1/5 (20%) 1 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Ejection fraction decreased 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Electrocardiogram QT corrected interval prolonged 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 2 0/10 (0%) 0 0/20 (0%) 0
Fibrinogen decreased 6/39 (15.4%) 6 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 2/22 (9.1%) 2 0/1 (0%) 0 2/20 (10%) 2 0/5 (0%) 0 2/49 (4.1%) 2 1/10 (10%) 1 0/20 (0%) 0
GGT increased 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Lipase increased 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 2 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Lymphocyte count decreased 39/39 (100%) 58 5/5 (100%) 5 2/2 (100%) 2 1/1 (100%) 2 18/18 (100%) 27 5/5 (100%) 7 21/22 (95.5%) 30 1/1 (100%) 1 20/20 (100%) 27 5/5 (100%) 8 48/49 (98%) 81 10/10 (100%) 14 19/20 (95%) 38
Lymphocyte count increased 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 2/22 (9.1%) 3 0/1 (0%) 0 1/20 (5%) 2 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 1/20 (5%) 2
Neutrophil count decreased 39/39 (100%) 59 5/5 (100%) 5 2/2 (100%) 2 1/1 (100%) 4 18/18 (100%) 25 5/5 (100%) 9 22/22 (100%) 34 1/1 (100%) 2 20/20 (100%) 29 5/5 (100%) 7 48/49 (98%) 68 10/10 (100%) 13 19/20 (95%) 31
Platelet count decreased 29/39 (74.4%) 52 5/5 (100%) 5 2/2 (100%) 2 1/1 (100%) 3 13/18 (72.2%) 17 5/5 (100%) 7 20/22 (90.9%) 28 1/1 (100%) 2 15/20 (75%) 17 4/5 (80%) 6 31/49 (63.3%) 43 5/10 (50%) 6 11/20 (55%) 18
Urine output decreased 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Weight gain 0/39 (0%) 0 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
White blood cell decreased 39/39 (100%) 56 5/5 (100%) 5 2/2 (100%) 2 1/1 (100%) 3 18/18 (100%) 24 5/5 (100%) 8 21/22 (95.5%) 31 1/1 (100%) 1 20/20 (100%) 29 5/5 (100%) 7 47/49 (95.9%) 67 10/10 (100%) 13 18/20 (90%) 28
Metabolism and nutrition disorders
Acidosis 0/39 (0%) 0 2/5 (40%) 2 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Alkalosis 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 2/10 (20%) 2 0/20 (0%) 0
Anorexia 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 1/5 (20%) 1 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 3/10 (30%) 3 0/20 (0%) 0
Dehydration 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hypercalcemia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hyperglycemia 9/39 (23.1%) 12 0/5 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 3/18 (16.7%) 3 1/5 (20%) 2 4/22 (18.2%) 5 1/1 (100%) 1 4/20 (20%) 4 0/5 (0%) 0 4/49 (8.2%) 5 2/10 (20%) 2 4/20 (20%) 4
Hyperkalemia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 1/20 (5%) 1
Hypermagnesemia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hyperuricemia 1/39 (2.6%) 1 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 2/22 (9.1%) 2 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Hypoalbuminemia 2/39 (5.1%) 2 3/5 (60%) 3 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 3/49 (6.1%) 3 1/10 (10%) 1 0/20 (0%) 0
Hypocalcemia 2/39 (5.1%) 2 4/5 (80%) 4 2/2 (100%) 2 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 9/22 (40.9%) 9 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 2/49 (4.1%) 2 1/10 (10%) 1 1/20 (5%) 1
Hypokalemia 5/39 (12.8%) 5 2/5 (40%) 2 1/2 (50%) 1 0/1 (0%) 0 4/18 (22.2%) 4 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 3/20 (15%) 3
Hypomagnesemia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Hyponatremia 7/39 (17.9%) 10 5/5 (100%) 5 1/2 (50%) 1 0/1 (0%) 0 9/18 (50%) 10 3/5 (60%) 4 11/22 (50%) 12 1/1 (100%) 1 4/20 (20%) 4 2/5 (40%) 2 21/49 (42.9%) 22 3/10 (30%) 4 7/20 (35%) 9
Hypophosphatemia 15/39 (38.5%) 16 5/5 (100%) 5 2/2 (100%) 2 0/1 (0%) 0 6/18 (33.3%) 6 1/5 (20%) 1 10/22 (45.5%) 11 1/1 (100%) 1 5/20 (25%) 5 0/5 (0%) 0 14/49 (28.6%) 16 7/10 (70%) 8 5/20 (25%) 5
Tumor lysis syndrome 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 1/1 (100%) 1 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Musculoskeletal and connective tissue disorders
Back pain 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 2 0/5 (0%) 0 2/49 (4.1%) 2 0/10 (0%) 0 1/20 (5%) 1
Bone pain 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 2/49 (4.1%) 2 0/10 (0%) 0 0/20 (0%) 0
Flank pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Generalized muscle weakness 4/39 (10.3%) 4 2/5 (40%) 2 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 0/22 (0%) 0 1/1 (100%) 1 2/20 (10%) 2 0/5 (0%) 0 2/49 (4.1%) 2 1/10 (10%) 1 0/20 (0%) 0
Muscle weakness left-sided 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Pain in extremity 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Nervous system disorders
Ataxia 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Cognitive disturbance 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Depressed level of consciousness 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Dysarthria 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Dysphasia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 2/20 (10%) 2
Encephalopathy 2/39 (5.1%) 2 2/5 (40%) 2 0/2 (0%) 0 0/1 (0%) 0 2/18 (11.1%) 2 0/5 (0%) 0 4/22 (18.2%) 4 1/1 (100%) 1 2/20 (10%) 2 2/5 (40%) 2 2/49 (4.1%) 2 2/10 (20%) 2 0/20 (0%) 0
Headache 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 4/18 (22.2%) 4 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 2/20 (10%) 2 1/5 (20%) 1 2/49 (4.1%) 2 1/10 (10%) 1 1/20 (5%) 1
Movements involuntary 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Nystagmus 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Peripheral motor neuropathy 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 1/5 (20%) 1 1/49 (2%) 1 1/10 (10%) 1 1/20 (5%) 1
Peripheral sensory neuropathy 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Somnolence 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Syncope 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 1/20 (5%) 1
Tremor 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Psychiatric disorders
Agitation 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Delirium 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Depression 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Insomnia 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 1/20 (5%) 1 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Personality change 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Renal and urinary disorders
Acute kidney injury 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 1/1 (100%) 1 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 1/10 (10%) 1 0/20 (0%) 0
Hematuria 0/39 (0%) 0 2/5 (40%) 2 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 1/20 (5%) 1
Urinary incontinence 1/39 (2.6%) 1 2/5 (40%) 2 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Reproductive system and breast disorders
Vaginal hemorrhage 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Respiratory, thoracic and mediastinal disorders
Apnea 0/39 (0%) 0 1/5 (20%) 1 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Aspiration 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/18 (5.6%) 1 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Dyspnea 4/39 (10.3%) 4 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 2 1/22 (4.5%) 1 1/1 (100%) 1 1/20 (5%) 1 0/5 (0%) 0 3/49 (6.1%) 3 3/10 (30%) 3 0/20 (0%) 0
Hypoxia 8/39 (20.5%) 8 4/5 (80%) 4 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 8/22 (36.4%) 8 1/1 (100%) 1 3/20 (15%) 3 0/5 (0%) 0 6/49 (12.2%) 7 2/10 (20%) 2 3/20 (15%) 3
Pleural effusion 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 1/5 (20%) 1 1/22 (4.5%) 1 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Pulmonary edema 2/39 (5.1%) 2 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 2/22 (9.1%) 2 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 1/20 (5%) 1
Skin and subcutaneous tissue disorders
Rash acneiform 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Rash maculo-papular 3/39 (7.7%) 4 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 4/22 (18.2%) 4 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Skin ulceration 1/39 (2.6%) 1 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Social circumstances
Menopause 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0
Vascular disorders
Hypertension 6/39 (15.4%) 6 2/5 (40%) 2 0/2 (0%) 0 0/1 (0%) 0 2/18 (11.1%) 2 2/5 (40%) 2 5/22 (22.7%) 8 0/1 (0%) 0 7/20 (35%) 10 1/5 (20%) 1 8/49 (16.3%) 11 2/10 (20%) 2 4/20 (20%) 5
Hypotension 12/39 (30.8%) 12 0/5 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 3/18 (16.7%) 4 1/5 (20%) 2 6/22 (27.3%) 8 0/1 (0%) 0 9/20 (45%) 9 2/5 (40%) 2 8/49 (16.3%) 10 2/10 (20%) 3 3/20 (15%) 3
Lymphedema 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 0/20 (0%) 0 0/5 (0%) 0 1/49 (2%) 1 0/10 (0%) 0 0/20 (0%) 0
Thromboembolic event 0/39 (0%) 0 0/5 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/18 (0%) 0 0/5 (0%) 0 0/22 (0%) 0 0/1 (0%) 0 2/20 (10%) 2 0/5 (0%) 0 0/49 (0%) 0 0/10 (0%) 0 0/20 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Jordan Gauthier
Organization Fred Hutchinson Cancer Research Center
Phone 206-667-2713
Email jgauthier@fredhutch.org
Responsible Party:
Alexandre Hirayama, Research Associate, Fred Hutchinson Cancer Center
ClinicalTrials.gov Identifier:
NCT01865617
Other Study ID Numbers:
  • 2639.00
  • NCI-2013-00073
  • 2639
  • RG9213011
  • P50CA107399
  • R01CA136551
First Posted:
May 31, 2013
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022