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NCT04160195

T Cells Expressing Fully-human Anti-CD19 and Anti-CD20 Chimeric Antigen Receptors for Treating B-cell Malignancies and Hodgkin Lymphoma

Terminated Phase 1 Results posted Last updated 15 February 2022
What this trial tests

Phase 1 trial testing Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells in Lymphoma, B-Cell in 2 participants. Terminated before completion.

Timeline
20 December 2019
Primary endpoint
11 June 2021
11 June 2021

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment2
Start date20 December 2019
Primary completion11 June 2021
Estimated completion11 June 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Lymphoma, B-Cell or Lymphoma, Non-hodgkins. 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 Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT) Primary · First protocol treatment through 28 days after the CAR T-cell infusion.

A DLT are defined as toxicities assessed by the Common Terminology Criteria for Adverse Events v5.0 that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.

Peripheral Motor Neuropathy Possibly Related
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation1
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase0
Guillain-Barre Syndrome Possibly Related
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation1
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase0
Percentage of Peak Blood Chimeric Antigen Receptors (CAR) T Cells Secondary · 119 days after CAR T-cell infusion

We measured CAR T-cell persistence by detecting the CAR gene in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR).

GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation10.5
Percentage of Peripheral Blood Mononuclear Cells (PBMC) of Chimeric Antigen Receptors (CAR) T Cells Secondary · pretreatment and multiple days from day 1 to day 173 after infusion.

Peak blood levels of Chimeric Antigen Receptors (CAR) T cells were measured by exact Wilcoxon rank sum test.

GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation10.47
Number of Participants With Clinical Response Secondary · Approximately 1 year 5 months

Response for lymphoma was assessed by the Revised Response Criteria for Malignant Lymphoma and The Lugano Classification. Complete Remission (CR) is complete disappearance of all detectable clinical evidence of disease. Partial Remission (PR) is ≥ 50% decrease in nodes or masses. Progressive Disease (PD) is Response ≥ 50% increase in a single node. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor PD. For participants with Chronic Lymphocytic Leukemia (CLL),response was assessed by the International Workshop on CLL. CR is no lymph nodes ≥ 1.5 cm on physical exam or rele

Complete Remission
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation0
Partial Remission
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation1
Progressive Disease
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation0
Stable Disease
GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation0
Last Time-Point at Which Chimeric Antigen Receptors (CAR) T Cells Were Detected in the Blood Secondary · 119 days after CAR T-cell infusion

Chimeric Antigen Receptors (CAR) T cell persistence was measured in the blood by quantitative polymerase chain reaction (PCR). CAR T cells that are detected in the participant's blood that persist for a significant length of time is a positive finding.

GroupValue95% CI
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation119
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · Date treatment consent signed to date off study, approximately 7 months and 18 days.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). 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
1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation1
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase0
Maximum Tolerated Dose (MTD) of Chimeric Antigen Receptors (CAR) T Cells Secondary · First protocol treatment through 28 days after the CAR T-cell infusion.

The maximum tolerated dose is the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT are defined as toxicities that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.

GroupValue95% CI
All ParticipantsNA

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 7 months and 18 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

1/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Dose Escalation
Serious: 1/1 (100%)
Deaths: 0/1
2/Conditioning Chemotherapy Plus Chimeric Antigen Receptors (CAR) T-cells Expansion Phase
Serious: 0
Deaths: 0

Serious adverse events (5 terms)

ReactionSystem1/Conditioning Chemotherap…2/Conditioning Chemotherap…
DysphagiaGastrointestinal disorders
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Peripheral motor neuropathyNervous system disorders
Peripheral sensory neuropathyNervous system disorders
TremorNervous system disorders
Other adverse events (21 terms — click to expand)

ReactionSystem1/Conditioning Chemotherap…2/Conditioning Chemotherap…
Alanine aminotransferase increasedInvestigations
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
FatigueGeneral disorders
FeverGeneral disorders
HeadacheNervous system disorders
HypertensionVascular disorders
HypoalbuminemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Lung infectionInfections and infestations
Lymphocyte count decreasedInvestigations
Lymphocyte count increasedInvestigations
Neutrophil count decreasedInvestigations
PainGeneral disorders
Peripheral motor neuropathyNervous system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Voice alterationRespiratory, thoracic and mediastinal disorders
White blood cell decreasedInvestigations

Most-reported serious reactions: Dysphagia, Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, Peripheral motor neuropathy, Peripheral sensory neuropathy, Tremor.

Data from ClinicalTrials.gov NCT04160195 adverse events section.

Sponsor's own description

Background: -Cluster of differentiation 19 (CD19) and cluster of differentiation 20 (CD20) are often found on certain cancer cells. Researchers think that a person's T cells can be modified in a lab to kill cells that have CD19 and CD20 on the surface. Objective: -To see if it is safe to give anti-CD19 and anti-CD20 CAR T cells to people with a B cell cancer or Hodgkin lymphoma. Eligibility: -People ages 18 and older with a B cell cancer or Hodgkin lymphoma that has not been controlled with standard therapies Design: * Participants will be screened under protocol 01C0129 with: * Medical history * Physical exam * Blood and heart tests * Bone marrow biopsy: A needle is inserted into the participant's hip bone to remove a small amount of marrow. Scans * Participants will have apheresis: Blood will be removed through a vein. The blood with circulate through a machine that removes the T cells. The rest of the blood will be returned to the participant. * Once a day for 3 days before they get the T cells, participants will receive chemotherapy through a vein. * Participants will receive the T cells through a vein. They will stay in the hospital for at least 9 days. * Participants may have a lumbar puncture: A needle will remove fluid from the spinal cord. * Participants may have a tumor biopsy. * Participants will repeat the screening tests throughout the study. * Participants will have follow-up visits 2 weeks after infusion; monthly for 4 months; at 6, 9, and 12 months; every 6 months for 3 years; and then annually for 5 years. Participants will then be contacted annually for 15 years.

Publications & conference data

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

  1. Assessing the Future of Solid Tumor Immunotherapy.
    Guha P, Heatherton KR, O'Connell KP, Alexander IS, et al · · 2022 · cited 85× · PMID 35327456 · DOI 10.3390/biomedicines10030655
  2. Next-generation chimeric antigen receptors for T- and natural killer-cell therapies against cancer.
    Li Y, Rezvani K, Rafei H. · · 2023 · cited 29× · PMID 37548050 · DOI 10.1111/imr.13255
  3. Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies.
    Keshavarz A, Salehi A, Khosravi S, Shariati Y, et al · · 2022 · cited 28× · PMID 36153626 · DOI 10.1186/s13287-022-03163-w
  4. Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.
    Zhao D, Zhu D, Cai F, Jiang M, et al · · 2023 · cited 12× · PMID 38037341 · DOI 10.1177/15330338231204198
  5. CAR-modified immune cells as a rapidly evolving approach in the context of cancer immunotherapies.
    Faeq MH, Al-Haideri M, Mohammad TAM, Gharebakhshi F, et al · · 2023 · cited 7× · PMID 37083979 · DOI 10.1007/s12032-023-02019-4
  6. The soldiers needed to be awakened: Tumor-infiltrating immune cells.
    Yaping W, Zhe W, Zhuling C, Ruolei L, et al · · 2022 · cited 5× · PMID 36246629 · DOI 10.3389/fgene.2022.988703

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