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NCT01593696

Anti-CD19 White Blood Cells for Children and Young Adults With B Cell Leukemia or Lymphoma

Completed Phase 1 Results posted Last updated 31 August 2020
What this trial tests

Phase 1 trial testing Anti-Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR) in ALL in 53 participants. Completed in 2 October 2017.

Timeline
29 June 2012
Primary endpoint
11 November 2016
2 October 2017

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment53
Start date29 June 2012
Primary completion11 November 2016
Estimated completion2 October 2017
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 1 to 30, any sex, with ALL or B Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Received Preparative Chemotherapy Followed by Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells With < Grade 4 Cytokine Release Syndrome Primary · Beginning of preparative regimen through Day 28 after CD19 CAR infusion

Participants with B cell malignancies who received preparative chemotherapy followed by CD19 CAR T-cells with \< Grade 4 cytokine release syndrome.

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)14
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)4
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)14
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)15
Number of Participants in Which the Prescribed Dose of Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR T-cells Were Successfully Manufactured Primary · Apheresis through completion of CAR manufacturing process, approximately 2 weeks

Participants who had T-cells collected by apheresis and subsequently had the amount of CAR T-cells manufactured as prescribed by the dose level they were enrolled in.

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)15
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)4
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0
Number of Participants Who Were Administered Intensive Chemotherapy Prior to Cluster of Differentiation (CD)19-Chimeric Antigen Receptor (CAR): CD19 CAR Infusion Secondary · 21 days of target date

Participants who were administered intensive chemotherapy prior to Cluster of Differentiation (CD)19-Chimeric antigen receptor (CAR): CD19 CAR infusion and received CAR cells within 21 days of the planned infusion date.

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)0
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)16
Mean Percentage Cluster of Differentiation 19 (CD19) - Chimeric Antigen-Receptor (CAR) T-Cells in Blood, Bone Marrow (BM) and Cerebrospinal Fluid (CSF) Secondary · 28 days (+/- 4 days) after infusion of CD19 CAR T-cells

Measure persistence of adoptively-transferred anti-CD19-CAR transduced T cells (defined by percent of CD19 CAR T-cells) in the blood and where possible the bone marrow and Cerebrospinal Fluid (CSF) of patients by flow cytometry assay.

Peripheral blood
GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.279± 0.712
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)0.122± 0.239
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.343± 1.022
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.897± 1.871
Bone marrow
GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.459± 0.781
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)0.554± 0.979
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.552± 1.308
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)0.814± 1.775
Cerebrospinal fluid
GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)3.186± 5.304
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)1.825± 2.943
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)7.192± 16.728
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)14.742± 16.301
Number of Patients With a Complete Response (CR) Secondary · Day 28 (+/- 4 days) after CD19 CAR infusion

Complete Response (CR) was assessed by bone marrow evaluation was I defined as \<5% leukemic blasts.

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)10
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)4
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)11
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)6
Number of Participants With Grade 4 Cytokine Release Syndrome (CRS) Secondary · Day 28 (+/- 4 days) after CD19 CAR infusion.

Participants with Grade 4 Cytokine Release Syndrome (CRS). CRS is defined as a clinical syndrome that may occur after cell therapy due to the release of cytokines (substances secreted by immune cells) into the body's blood stream.

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)2
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)1
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)1
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)1
Number of Participants With Serious and Non-Serious Adverse Events Secondary · Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one

GroupValue95% CI
Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)16
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)5
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)16
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)16

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, from 1.5 months up to 3.1 years.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)
Serious: 6/16 (38%)
Deaths: 10/16
Phase 1, Arm 2 - 3 x 10E6 Transduced T Cells/kg (+/- 20%)
Serious: 2/5 (40%)
Deaths: 3/5
Phase 2, Arm 1 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)
Serious: 1/16 (6%)
Deaths: 5/16
Phase 2, Arm 2 - 1 x 10E6 Transduced T Cells/kg (+/- 20%)
Serious: 5/16 (31%)
Deaths: 11/16

Serious adverse events (28 terms)

ReactionSystemPhase 1, Arm 1 - 1 x 10E6 …Phase 1, Arm 2 - 3 x 10E6 …Phase 2, Arm 1 - 1 x 10E6 …Phase 2, Arm 2 - 1 x 10E6 …
Cytokine release syndromeImmune system disorders
SeizureNervous system disorders
Sinus tachycardiaCardiac disorders
DysphasiaNervous system disorders
FeverGeneral disorders
HeadacheNervous system disorders
HypotensionVascular disorders
MyalgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Cardiac arrestCardiac disorders
Cardiac disorders - Other, biventricular dilatationCardiac disorders
Heart failureCardiac disorders
HydrocephalusNervous system disorders
HypertensionVascular disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Left ventricular systolic dysfunctionCardiac disorders
Nervous system disorders - Other, L deviated gazeNervous system disorders
Nervous system disorders - Other, increased ventricle sizeNervous system disorders
Neutrophil count decreasedInvestigations
Pulmonary edemaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
SomnolenceNervous system disorders
Cardiac disorders - Other, dilated cardiomyopathyCardiac disorders
Cardiac disorders - Other, elevated RVSPCardiac disorders
Cardiac disorders - Other, global systolic dysfunctionCardiac disorders
Other adverse events (254 terms — click to expand)

ReactionSystemPhase 1, Arm 1 - 1 x 10E6 …Phase 1, Arm 2 - 3 x 10E6 …Phase 2, Arm 1 - 1 x 10E6 …Phase 2, Arm 2 - 1 x 10E6 …
Lymphocyte count decreasedInvestigations
White blood cell decreasedInvestigations
FeverGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Activated partial thromboplastin time prolongedInvestigations
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
HypokalemiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
PainGeneral disorders
Alanine aminotransferase increasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
Cytokine release syndromeImmune system disorders
HypocalcemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
DiarrheaGastrointestinal disorders
VomitingGastrointestinal disorders
Weight gainInvestigations
HeadacheNervous system disorders
HypertensionVascular disorders
Sinus tachycardiaCardiac disorders
HypernatremiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
AnxietyPsychiatric disorders
HypotensionVascular disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
HypercalcemiaMetabolism and nutrition disorders
HyperuricemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
Respiratory, thoracic and mediastinal disorders - Other, TachypneaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
AnorexiaMetabolism and nutrition disorders

Most-reported serious reactions: Cytokine release syndrome, Seizure, Sinus tachycardia, Dysphasia, Fever, Headache, Hypotension, Myalgia.

Data from ClinicalTrials.gov NCT01593696 adverse events section.

Sponsor's own description

Background: \- Although progress has been made in treating children with B-cell cancers such as leukemia or lymphoma, many children do not respond to the standard treatments. One possible treatment involves collecting white blood cells called T cells from the person with cancer and modifying the cells to attack the B-cell cancer. The cells can then be given back to the participant. This study will use T cells that have been modified to attack the cluster of differentiation 19 (CD19) protein, which is found on the surface of some B-cell cancers. Objectives: \- To see if anti-CD19 modified white blood cells are a safe and effective treatment for children and young adults with advanced B-cell cancer. Eligibility: * Children and young adults between 1 and 30 years of age who have B-cell cancer (leukemia or lymphoma) that has not responded to standard treatments. * The leukemia or the lymphoma must have the CD19 protein. * There must be adequate organ function. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow biopsies may be performed depending on the type of cancer. * Participants will undergo a process where white blood cells are collected, called apheresis. These cells will be modified to contain the anti-CD19 gene. * Participants will have 3 days of chemotherapy to prepare their immune system to accept the modified cells. * Participants will receive an infusion of their own modified white blood cells. They will remain in the hospital until they have recovered from the treatment. * Participants will have frequent follow-up visits to monitor the outcome of the treatment. * If the participant benefits from the treatment, then he/she may have the option for another round of treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.
    Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, et al · · 2015 · cited 2298× · PMID 25319501 · DOI 10.1016/s0140-6736(14)61403-3
  2. Engineered T cells: the promise and challenges of cancer immunotherapy.
    Fesnak AD, June CH, Levine BL. · · 2016 · cited 812× · PMID 27550819 · DOI 10.1038/nrc.2016.97
  3. Antibody-modified T cells: CARs take the front seat for hematologic malignancies.
    Maus MV, Grupp SA, Porter DL, June CH. · · 2014 · cited 474× · PMID 24578504 · DOI 10.1182/blood-2013-11-492231
  4. Driving CAR T-cells forward.
    Jackson HJ, Rafiq S, Brentjens RJ. · · 2016 · cited 457× · PMID 27000958 · DOI 10.1038/nrclinonc.2016.36
  5. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.
    Kochenderfer JN, Rosenberg SA. · · 2013 · cited 351× · PMID 23546520 · DOI 10.1038/nrclinonc.2013.46
  6. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity.
    Jacoby E, Nguyen SM, Fountaine TJ, Welp K, et al · · 2016 · cited 350× · PMID 27460500 · DOI 10.1038/ncomms12320
  7. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL.
    Shah NN, Lee DW, Yates B, Yuan CM, et al · · 2021 · cited 277× · PMID 33764809 · DOI 10.1200/jco.20.02262
  8. Engineered T Cell Therapy for Cancer in the Clinic.
    Zhao L, Cao YJ. · · 2019 · cited 275× · PMID 31681259 · DOI 10.3389/fimmu.2019.02250

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01593696.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing