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NCT01583686

CAR T Cell Receptor Immunotherapy Targeting Mesothelin for Patients With Metastatic Cancer

Terminated Phase 1, PHASE2 Results posted Last updated 14 October 2019
What this trial tests

Phase 1, PHASE2 trial testing Fludarabine in Cervical Cancer in 15 participants. Terminated before completion.

Timeline
4 May 2012
Primary endpoint
17 December 2018
17 December 2018

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment15
Start date4 May 2012
Primary completion17 December 2018
Estimated completion17 December 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 Cervical Cancer or Pancreatic 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 · 3.5 mos.

Objective tumor regression response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.0. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of the longest diameter (LD) of target le

GroupValue95% CI
Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-20
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-20
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-20
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-20
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-20
Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-20
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-20
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-20
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-20
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-20
Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-20
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-21
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-20
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-20
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-20
Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-23
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-22
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-23
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-23
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-23
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Primary · Date treatment consent signed to date off study, approximately 6 months and 17 days for Group A01, 16 months and 13 days for Group A02, 13 months and 3 days for Group A03, 10 months and 16 days for Group A04, and 11 months and 26 days for Group A05.

Here is the count 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 o

GroupValue95% CI
Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-23
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-23
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-23
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-23
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-23

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 6 months and 17 days for Group A01, 16 months and 13 days for Group A02, 13 months and 3 days for Group A03, 10 months and 16 days for Group A04, and 11 months and 26 days for Group A05.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A01 Anti-mesothelin CAR PBL 1x10^6 + IL-2
Serious: 1/3 (33%)
Deaths: 0/3
Arm A02 Anti-mesothelin CAR PBL 3x10^6 + IL-2
Serious: 2/3 (67%)
Deaths: 0/3
Arm A03 Anti-mesothelin CAR PBL 1x10^7 + IL-2
Serious: 0/3 (0%)
Deaths: 0/3
Arm A04 Anti-mesothelin CAR PBL 3x10^7 + IL-2
Serious: 1/3 (33%)
Deaths: 0/3
Arm A05 Anti-mesothelin CAR PBL 1x10^8 + IL-2
Serious: 2/3 (67%)
Deaths: 1/3

Serious adverse events (5 terms)

ReactionSystemArm A01 Anti-mesothelin CA…Arm A02 Anti-mesothelin CA…Arm A03 Anti-mesothelin CA…Arm A04 Anti-mesothelin CA…Arm A05 Anti-mesothelin CA…
ConstipationGastrointestinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Platelet count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
Lymphocyte count decreasedInvestigations
Other adverse events (21 terms — click to expand)

ReactionSystemArm A01 Anti-mesothelin CA…Arm A02 Anti-mesothelin CA…Arm A03 Anti-mesothelin CA…Arm A04 Anti-mesothelin CA…Arm A05 Anti-mesothelin CA…
Fatigue (asthenia, lethargy, malaise)General disorders
White blood cell count decreasedInvestigations
LymphopeniaInvestigations
Neutrophils/granulocytes (ANC/AGC) count decreasedInvestigations
PlateletsInvestigations
HypoxiaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)Investigations
Pain: Abdomen NOSGastrointestinal disorders
Infection with unknown ANC: Nerve-peripheralInfections and infestations
Albumin (hypoalbuminemia)Metabolism and nutrition disorders
PsychosisPsychiatric disorders
Supraventricular and nodal arrhythmia: Sinus tachycardiaCardiac disorders
Thrombosis/embolism (vascular access related)Vascular disorders
InfectionInfections and infestations
Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)Investigations
Magnesium, serum-high (hypermagnesemia)Investigations
PTT (Partial Thromboplastin Time)Investigations
TRALIGeneral disorders
Phosphate, serum-lowMetabolism and nutrition disorders

Most-reported serious reactions: Constipation, Hypoxia, Platelet count decreased, Anemia, Lymphocyte count decreased.

Data from ClinicalTrials.gov NCT01583686 adverse events section.

Sponsor's own description

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with metastatic 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-mesothelin 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 tumor fighting cells (anti-mesothelin cells) cause metastatic cancer tumors to shrink. Eligibility: \- Adults age 18-70 with metastatic cancer expressing the mesothelin 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-mesothelin 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-mesothelin 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 will take up to 2 days.

Publications & conference data

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

  1. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition.
    Cherkassky L, Morello A, Villena-Vargas J, Feng Y, et al · · 2016 · cited 856× · PMID 27454297 · DOI 10.1172/jci83092
  2. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment.
    Martinez M, Moon EK. · · 2019 · cited 653× · PMID 30804938 · DOI 10.3389/fimmu.2019.00128
  3. Driving CAR T-cells forward.
    Jackson HJ, Rafiq S, Brentjens RJ. · · 2016 · cited 457× · PMID 27000958 · DOI 10.1038/nrclinonc.2016.36
  4. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies.
    Adamska A, Domenichini A, Falasca M. · · 2017 · cited 429× · PMID 28640192 · DOI 10.3390/ijms18071338
  5. Genetics and biology of pancreatic ductal adenocarcinoma.
    Ying H, Dey P, Yao W, Kimmelman AC, et al · · 2016 · cited 419× · PMID 26883357 · DOI 10.1101/gad.275776.115
  6. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  7. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors.
    Morello A, Sadelain M, Adusumilli PS. · · 2016 · cited 402× · PMID 26503962 · DOI 10.1158/2159-8290.cd-15-0583
  8. CAR T cells in solid tumors: challenges and opportunities.
    Marofi F, Motavalli R, Safonov VA, Thangavelu L, et al · · 2021 · cited 394× · PMID 33494834 · DOI 10.1186/s13287-020-02128-1

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Other trials of Fludarabine

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Trials by the same sponsor.

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