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NCT02153905

T Cell Receptor Immunotherapy Targeting MAGE-A3 for Patients With Metastatic Cancer Who Are HLA-A*01 Positive

Terminated Phase 1, PHASE2 Results posted Last updated 17 June 2019
What this trial tests

Phase 1, PHASE2 trial testing Aldesleukin in Breast Cancer in 3 participants. Terminated before completion.

Timeline
3 July 2014
Primary endpoint
10 September 2018
10 September 2018

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment3
Start date3 July 2014
Primary completion10 September 2018
Estimated completion10 September 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 70, any sex, with Breast Cancer or Cervical Cancer. 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 Patients With Objective Tumor Regression Primary · 6 and 12 weeks after cell infusion on up to 2 years

Objective tumor regression is defined as the number of participants with a complete or partial response per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Complete Response
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)0
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Partial Response
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)0
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)1
Number of Treatment Related Adverse Events Related to T-Cell Receptor (TCR) Gene-Engineered Cells Primary · Date treatment consent signed to end of treatment, approximately 30 days

Aggregate of all Grade ≥3 adverse events and their frequency possibly, probably or definitely related to the research. Adverse Events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Grade 3 is severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL). Grade 4 is life-threatening consequences; urgent intervention indicated. Grade 5 is death related to adverse event.

Grade 3 Atrial Fibrillation
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Diarrhea
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Ileus
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Edema face: anasarca
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Fibrinogen decreased
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 aPTT prolonged
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Acute Kidney Injury
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Grade 3 Rash maculo-papular
GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0
Number of Participants With Serious and Non-Serious Adverse Events Primary · Date treatment consent signed to date off study, approximately 53 days for the Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2) Arm/Group, and 1 year and 4 months for the Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2) Arm/Group.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)2
Number of Participants With Dose-Limiting Toxicity (DLT) Secondary · Within 30 days of study cell infusion

DLT is defined as follows: Grade 3-5 allergic reactions related to the study cell infusion. Grade 3 and greater autoimmune reactions. Grades 3 and greater organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 30 days of study cell infusion and does not resolve within 72 hours. Treatment-related death within 8 weeks of the study cell infusion.

GroupValue95% CI
Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)0

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 53 days for the Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2) Arm/Group, and 1 year and 4 months for the Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2) Arm/Group.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Anti-MAGE-A3 A1 TCR PBL 1x10^9 Cells + Interleukin-2 (IL-2)
Serious: 1/1 (100%)
Deaths: 1/1
Anti-MAGE-A3 A1 TCR PBL 1x10^8 Cells + Interleukin-2 (IL-2)
Serious: 1/2 (50%)
Deaths: 0/2

Serious adverse events (8 terms)

ReactionSystemAnti-MAGE-A3 A1 TCR PBL 1x…Anti-MAGE-A3 A1 TCR PBL 1x…
Edema: head and neckGeneral disorders
EncephalopathyNervous system disorders
Hemorrhage, GI::Abdomen NOSGastrointestinal disorders
HypotensionVascular disorders
Renal failureRenal and urinary disorders
Somnolence/depressed level of consciousnessNervous system disorders
Syndromes - Other (Specify, hemophagocytic syndrome)Immune system disorders
Infection (documented clinically or microbiologically)Infections and infestations
Other adverse events (20 terms — click to expand)

ReactionSystemAnti-MAGE-A3 A1 TCR PBL 1x…Anti-MAGE-A3 A1 TCR PBL 1x…
HemoglobinInvestigations
LymphopeniaInvestigations
Neutrophils/granulocytes (ANC/AGC)Investigations
PlateletsInvestigations
Allergic reaction/hypersensitivity (including drug fever)Immune system disorders
Bilirubin (hyperbilirubinemia)Investigations
CreatinineInvestigations
DiarrheaGastrointestinal disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)General disorders
FibrinogenInvestigations
Ileus, GI (functional obstruction of bowel, i.e., neuro-constipation)Gastrointestinal disorders
Infection with normal ANC or Grade 1 or 2 neutrophils::BloodInfections and infestations
Infection (documented clinically or microbiologically)Infections and infestations
Leukocytes (total WBC)Investigations
PTT (Partial Thromboplastin Time)Investigations
Pleural effusion (non-malignant)Respiratory, thoracic and mediastinal disorders
Rash/desquamationSkin and subcutaneous tissue disorders
Supraventricular and nodal arrhythmia::Atrial fibrillationCardiac disorders
ConfusionPsychiatric disorders
Psychosis (hallucinations/delusions)Psychiatric disorders

Most-reported serious reactions: Edema: head and neck, Encephalopathy, Hemorrhage, GI::Abdomen NOS, Hypotension, Renal failure, Somnolence/depressed level of consciousness, Syndromes - Other (Specify, hemophagocytic syndrome), Infection (documented clinically or microbiologically).

Data from ClinicalTrials.gov NCT02153905 adverse events section.

Sponsor's own description

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patients white blood cells with a retrovirus that has the gene for anti-MAGE-A3 incorporated in the retrovirus. Objective: The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (anti-MAGE A3 cells) cause tumors to shrink and to be certain the treatment is safe Eligibility: \- Adults age 18-66 with cancer expressing the MAGE-A3 molecule. Design: * Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed * Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti MAGE-A3 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.} * Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti MAGE-A3 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Publications & conference data

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

  1. 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
  2. Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy.
    Pol J, Vacchelli E, Aranda F, Castoldi F, et al · · 2015 · cited 238× · PMID 26137404 · DOI 10.1080/2162402x.2015.1008866
  3. Driving gene-engineered T cell immunotherapy of cancer.
    Johnson LA, June CH. · · 2017 · cited 211× · PMID 28025979 · DOI 10.1038/cr.2016.154
  4. Heterogeneity of the tumor immune microenvironment and its clinical relevance.
    Jia Q, Wang A, Yuan Y, Zhu B, et al · · 2022 · cited 176× · PMID 35461288 · DOI 10.1186/s40164-022-00277-y
  5. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.
    Tsimberidou AM, Van Morris K, Vo HH, Eck S, et al · · 2021 · cited 119× · PMID 34193217 · DOI 10.1186/s13045-021-01115-0
  6. Synthetic biology in cell-based cancer immunotherapy.
    Chakravarti D, Wong WW. · · 2015 · cited 55× · PMID 26088008 · DOI 10.1016/j.tibtech.2015.05.001
  7. TCR engineered T cells for solid tumor immunotherapy.
    Zhang Y, Liu Z, Wei W, Li Y. · · 2022 · cited 46× · PMID 35725570 · DOI 10.1186/s40164-022-00291-0
  8. Strategies to genetically engineer T cells for cancer immunotherapy.
    Spear TT, Nagato K, Nishimura MI. · · 2016 · cited 44× · PMID 27138532 · DOI 10.1007/s00262-016-1842-5

Verify or expand the search:

Other trials of Aldesleukin

Trials testing the same drug.

Other recruiting trials for Breast Cancer

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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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/NCT02153905.

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