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NCT02706392

Genetically Modified T-Cell Therapy in Treating Patients With Advanced ROR1+ Malignancies

Terminated Phase 1 Results posted Last updated 31 August 2022
What this trial tests

Phase 1 trial testing Laboratory Biomarker Analysis in Hematopoietic and Lymphoid Cell Neoplasm in 21 participants. Terminated before completion.

Timeline
16 March 2016
Primary endpoint
17 May 2021
28 September 2021

Quick facts

Lead sponsorFred Hutchinson Cancer Center
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment21
Start date16 March 2016
Primary completion17 May 2021
Estimated completion28 September 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Hematopoietic and Lymphoid Cell Neoplasm or Malignant Solid Neoplasm. 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 That Experienced Adverse Events Primary · Within 35 days of receptor tyrosine kinase-like orphan receptor 1 positive chimeric antigen receptor-T cell infusion

Will be graded according to Common Terminology Criteria for Adverse Events. Outcome will be reported as a count of participants that experienced adverse events in each arm.

GroupValue95% CI
Cohort A Dose Level 12
Cohort A Dose Level 21
Cohort B Dose Level 12
Cohort B Dose Level 23
Cohort B Dose Level 311
Cohort B Dose Level 42
Number of Participants With Persistence of Adoptively Transferred Receptor Tyrosine Kinase-like Orphan Receptor 1 Positive Chimeric Antigen Receptor-T Cells Secondary · Up to 28 days after the T cell infusion

Data should be collected for persistence of transferred T cells and descriptive statistics will be used to summarize the changes from baseline where possible. This outcome is reported as a count of participants who experienced persistence at Day 28.

GroupValue95% CI
Cohort A Dose Level 12
Cohort A Dose Level 20
Cohort B Dose Level 12
Cohort B Dose Level 21
Cohort B Dose Level 30
Cohort B Dose Level 40
Number of Participants Biopsied With Detectable CD3 T-cells Secondary · Up to 48 days post infusion

Samples of bone marrow, blood and other tissues (e.g. cerebral spinal fluid, tumor, thoracentesis fluid) will be collected from patients as clinically indicated. CD3 T-cells and their frequency/persistence will be detected by flow cytometry, polymerase chain reaction, and immunohistochemistry as appropriate. This outcome is reported as a count of participants who had detectable CD3 T-cells in their biopsy sample. The patients in Cohort A had a biopsy of their bone marrow. For the patients in Cohort B, biopsy location was dependent on site of disease per patient.

GroupValue95% CI
Cohort A Dose Level 12
Cohort A Dose Level 20
Cohort B Dose Level 12
Cohort B Dose Level 21
Cohort B Dose Level 30
Cohort B Dose Level 40
Objective Response Rate of Complete Remission and Partial Remission Secondary · Up to 1 year

Outcome will be reported as a count of participants in each arm that experienced complete remission and/or partial remission. For Patients with Acute lymphoblast leukemia (ALL), remission status will be determined by restaging of bone marrow and other involved sites by morphology, flow cytometry and molecular studies, as appropriate. For Patients with NSCLC and TNBC, tumor response and progression will be evaluated in this study using the international criteria proposed by RECIST Criteria. Target lesion responses will be described as (1) Complete response (CR): disappearance of all target lesi

GroupValue95% CI
Cohort A Dose Level 10
Cohort A Dose Level 20
Cohort B Dose Level 10
Cohort B Dose Level 21
Cohort B Dose Level 30
Cohort B Dose Level 40
Progression Free Survival Secondary · Up to 1 year

Outcome will be reported as a count of participants in each arm that survived up to 1 year post-infusion (per patient) and did not progress. For patients with Acute lymphoblast leukemia (ALL), remission status will be determined by restaging of bone marrow and other involved sites by morphology, flow cytometry and molecular studies, as appropriate. For Patients with NSCLC and TNBC, tumor response and progression will be evaluated in this study using the international criteria proposed by RECIST Criteria. Target lesion responses will be described as (1) Complete response (CR): disappearance of

GroupValue95% CI
Cohort A Dose Level 10
Cohort A Dose Level 20
Cohort B Dose Level 10
Cohort B Dose Level 20
Cohort B Dose Level 31
Cohort B Dose Level 40
Overall Survival Secondary · Up to 1 year

Data should be collected for efficacy of transferred T cells and descriptive statistics will be used to summarize the changes from baseline where possible. Outcome will be reported as a count of participants that survived up until the 1 year post-infusion (per patient) timepoint.

GroupValue95% CI
Cohort A Dose Level 11
Cohort A Dose Level 21
Cohort B Dose Level 10
Cohort B Dose Level 21
Cohort B Dose Level 36
Cohort B Dose Level 40

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to one year following last infusion per patient. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A Dose Level 1
Serious: 1/2 (50%)
Deaths: 1/2
Cohort A Dose Level 2
Serious: 1/1 (100%)
Deaths: 0/1
Cohort B Dose Level 1
Serious: 1/2 (50%)
Deaths: 2/2
Cohort B Dose Level 2
Serious: 2/3 (67%)
Deaths: 2/3
Cohort B Dose Level 3
Serious: 10/11 (91%)
Deaths: 5/11
Cohort B Dose Level 4
Serious: 2/2 (100%)
Deaths: 2/2

Serious adverse events (11 terms)

ReactionSystemCohort A Dose Level 1Cohort A Dose Level 2Cohort B Dose Level 1Cohort B Dose Level 2Cohort B Dose Level 3Cohort B Dose Level 4
FeverGeneral disorders
Cytokine release syndromeImmune system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Febrile neutropeniaBlood and lymphatic system disorders
Non-cardiac chest painGeneral disorders
FallInjury, poisoning and procedural complications
MyalgiaMusculoskeletal and connective tissue disorders
EncephalopathyNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (36 terms — click to expand)

ReactionSystemCohort A Dose Level 1Cohort A Dose Level 2Cohort B Dose Level 1Cohort B Dose Level 2Cohort B Dose Level 3Cohort B Dose Level 4
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
White blood cell decreasedInvestigations
AnemiaBlood and lymphatic system disorders
HypophosphatemiaMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
HypoxiaRespiratory, thoracic and mediastinal disorders
HyponatremiaMetabolism and nutrition disorders
Sinus tachycardiaCardiac disorders
FatigueGeneral disorders
Activated partial thromboplastin time prolongedInvestigations
Pulmonary edemaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
ConstipationGastrointestinal disorders
Edema limbsGeneral disorders
Cytokine release syndromeImmune system disorders
Lung infectionInfections and infestations
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Fibrinogen decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
HyperglycemiaMetabolism and nutrition disorders
HyperkalemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
SomnolenceNervous system disorders
AgitationPsychiatric disorders
DeliriumPsychiatric disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
HyperuricemiaMetabolism and nutrition disorders

Most-reported serious reactions: Fever, Cytokine release syndrome, Hypoxia, Hypotension, Febrile neutropenia, Non-cardiac chest pain, Fall, Myalgia.

Data from ClinicalTrials.gov NCT02706392 adverse events section.

Sponsor's own description

This phase I trial studies the side effects and best dose of genetically modified T-cell therapy in treating patients with receptor tyrosine kinase-like orphan receptor 1 positive (ROR1+) chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), stage IV non-small cell lung cancer (NSCLC), or triple negative breast cancer (TNBC) that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Genetically modified therapies, such as ROR1 specific chimeric antigen receptor (CAR) T-cells, are taken from a patient's blood, modified in the laboratory so they specifically may kill cancer cells with a protein called ROR1 on their surfaces, and safely given back to the patient after conventional therapy. The "genetically modified" T-cells have genes added in the laboratory to make them recognize ROR1.

Publications & conference data

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

  1. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances.
    Maalej KM, Merhi M, Inchakalody VP, Mestiri S, et al · · 2023 · cited 421× · PMID 36717905 · DOI 10.1186/s12943-023-01723-z
  2. Chimeric antigen receptor T-cell therapies for lymphoma.
    Brudno JN, Kochenderfer JN. · · 2018 · cited 390× · PMID 28857075 · DOI 10.1038/nrclinonc.2017.128
  3. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.
    Ye F, Dewanjee S, Li Y, Jha NK, et al · · 2023 · cited 361× · PMID 37415164 · DOI 10.1186/s12943-023-01805-y
  4. CAR-T cells: the long and winding road to solid tumors.
    D'Aloia MM, Zizzari IG, Sacchetti B, Pierelli L, et al · · 2018 · cited 311× · PMID 29449531 · DOI 10.1038/s41419-018-0278-6
  5. Engineered T Cell Therapy for Cancer in the Clinic.
    Zhao L, Cao YJ. · · 2019 · cited 275× · PMID 31681259 · DOI 10.3389/fimmu.2019.02250
  6. Logic-Gated ROR1 Chimeric Antigen Receptor Expression Rescues T Cell-Mediated Toxicity to Normal Tissues and Enables Selective Tumor Targeting.
    Srivastava S, Salter AI, Liggitt D, Yechan-Gunja S, et al · · 2019 · cited 271× · PMID 30889382 · DOI 10.1016/j.ccell.2019.02.003
  7. Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade.
    Srivastava S, Furlan SN, Jaeger-Ruckstuhl CA, Sarvothama M, et al · · 2021 · cited 252× · PMID 33357452 · DOI 10.1016/j.ccell.2020.11.005
  8. Driving gene-engineered T cell immunotherapy of cancer.
    Johnson LA, June CH. · · 2017 · cited 211× · PMID 28025979 · DOI 10.1038/cr.2016.154

Verify or expand the search:

Other trials of Laboratory Biomarker Analysis

Trials testing the same drug.

Other recruiting trials for Hematopoietic and Lymphoid Cell Neoplasm

Currently open trials in the same condition.

Other Fred Hutchinson Cancer Center trials

Trials by the same sponsor.

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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/NCT02706392.

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