MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers

NCT ID: NCT02989064

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-31

Study Completion Date

2020-06-04

Brief Summary

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This Phase 1 study is designed as a cell dose escalation trial in HLA-A\*02:01 and HLA-A\*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose.

The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer.

Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.

Detailed Description

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Conditions

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Urothelial Carcinoma Head and Neck Cancer Melanoma Bladder Urothelial Carcinoma

Keywords

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Cell Therapy T Cell Therapy SPEAR T Cell MAGE-A10 Immuno-oncology Metastatic Urothelial Cancer Previously Treated T Cell Receptor Inoperable Advanced Cancer Bladder Head and neck Melanoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells

Group Type EXPERIMENTAL

Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells

Intervention Type GENETIC

Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1

Interventions

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Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells

Infusion of autologous genetically modified MAGE A10ᶜ⁷⁹⁶T on Day 1

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

1. Subject is ≥18 to ≤75 years of age at the time of signing the study informed consent.
2. Subject has histologically confirmed diagnosis of any one of the following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
3. Subject is HLA-A\*02:01 and/or HLA-A\*02:06 positive.
4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
5. Subject meets disease-specific requirements per protocol
6. Subject has anticipated life expectancy \> 6 months prior to leukapheresis and \>3 months prior to lymphodepletion.
7. Subject's tumor shows positive MAGE-A10 expression
8. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
9. Subject has a left ventricular ejection fraction ≥50%.
10. Subject is fit for leukapheresis and has adequate venous access for the cell collection.
11. Female subject of childbearing potential (FCBP) must have a negative urine or serum pregnancy test or male subject must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter.
12. Subject must have adequate organ function per protocol

Exclusion Criteria

1. Subject is HLA-A\*02:05 in either allele, HLA-B\*15:01 and/or HLA-B\*46:01 positive. Subject has any A\*02 null allele (designated with an "N", e.g. A\*02:32N) as the sole HLA-A\*02 allele.
2. Subject has received or plans to receive excluded therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy per protocol
3. Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment
4. Subject has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
5. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
6. Subject has an electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with bundle branch block \[BBB\]) over 3 consecutive ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.
7. Subject has symptomatic CNS metastases.
8. Subject has a history of chronic or recurrent severe autoimmune or immune mediated disease
9. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening.
10. Subject has uncontrolled intercurrent illness
11. Subject has active infection with HIV, HBV, HCV or HTLV
12. Subject is pregnant or breastfeeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Adaptimmune

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Hong, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Washington University - School of Medicine

St Louis, Missouri, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Tennessee Oncology - Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Start Madrid-FJD, Fundación Jimѐnez Díaz

Madrid, , Spain

Site Status

Hospital Universitario 12 Octubre Avda. de Córdoba

Madrid, , Spain

Site Status

Countries

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United States Canada Spain

References

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Hong DS, Butler MO, Pachynski RK, Sullivan R, Kebriaei P, Boross-Harmer S, Ghobadi A, Frigault MJ, Dumbrava EE, Sauer A, Brophy F, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou DG, Wang R, Solis LM, Duose DY, Sanderson JP, Gerry AB, Marks D, Bai J, Norry E, Fracasso PM. Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. Front Oncol. 2022 Mar 18;12:818679. doi: 10.3389/fonc.2022.818679. eCollection 2022.

Reference Type DERIVED
PMID: 35372008 (View on PubMed)

Other Identifiers

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ADP-0022-004

Identifier Type: -

Identifier Source: org_study_id