Clinical Trial - NCT02989064

MAGE-A10¿7¿6T for Urothelial Cancer, Melanoma or Head and Neck Cancers

Active, not recruiting

Sponsor: Adaptimmune

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02989064

Protocol Info

Short Description: Phase 1 MAGE-A10C796T in Urothelial, Melanoma or Head/Neck Tumors
Long Description: Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10C796T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors
MGH Status: Open
Sponsor: Adaptimmune
Disease Program: Cellular

Next Steps


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Purpose

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-A10¿7¿6T 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.
Condition Title Intervention Phase
Urothelial Carcinoma Head and Neck Cancer Melanoma Bladder Urothelial Carcinoma Autologous genetically modified MAGE A10¿7¿6T cell Phase 1
Study Type Interventional
Official Title Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10¿7¿6T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors

Primary Outcome Measures

Number of subjects with adverse events (AE), including serious adverse events (SAE). [Time Frame: 3 years] [Designated as safety issue: ]

Evaluation of the persistence of genetically modified T cells [Time Frame: 3 years] [Designated as safety issue: ]

Measurement of RCL in genetically modified T cells. [Time Frame: 3 years] [Designated as safety issue: ]

Assessment of dose limiting toxicities to determine optimally tolerated dose range [Time Frame: 3 years] [Designated as safety issue: ]

Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR). [Time Frame: 3 years] [Designated as safety issue: ]

Interval between the date of first T cell infusion dose and first documented evidence of CR or PR. [Time Frame: 3 years] [Designated as safety issue: ]

Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause. [Time Frame: 3 years] [Designated as safety issue: ]

Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause. [Time Frame: 3 years] [Designated as safety issue: ]

Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [Time Frame: 3 years] [Designated as safety issue: ]

Interval between the date of first T cell infusion and date of death due to any cause. [Time Frame: 3 years] [Designated as safety issue: ]

Number and % of subjects having any Long Term Follow Up Adverse Events (AEs) [Time Frame: 15 years post last treatment (infusion)] [Designated as safety issue: ]


Secondary Outcome Measures

Estimated Enrollment: 10
Study Start Date: October 2016
Estimated Study Completion Date: November 2034
Estimated Primary Completion Date: December 2019
Arms Assigned Interventions

Experimental:Autologous genetically modified MAGE A10¿7¿6T cells

Genetic:Autologous genetically modified MAGE A10¿7¿6T cells
Infusion of autologous genetically modified MAGE A10¿7¿6T on Day 1

Eligibility

Ages Eligible for Study: 75 Years-75 Years

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02989064

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
  • United States, Missouri
    • Washington University - School of Medicine Saint Louis, Missouri, United States, 63110
  • United States, New York
    • Roswell Park Cancer Institute Buffalo, New York, United States, 14263
  • United States, Ohio
    • Ohio State University Wexner Medical Center Columbus, Ohio, United States, 43210
  • United States, Pennsylvania
    • Fox Chase Cancer Center Philadelphia, Pennsylvania, United States, 19111
  • United States, Tennessee
    • Tennessee Oncology - Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
    • Vanderbilt - Ingram Cancer Center Nashville, Tennessee, United States, 37203
  • United States, Texas
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • Canada, Ontario
    • Princess Margaret Cancer Centre Toronto, Ontario, Canada, M5G1X6
  • Spain,
    • Start Madrid-FJD, Fundación Jim¿nez Díaz Madrid, , Spain, 28040
    • Hospital Universitario 12 Octubre Avda. de Córdoba Madrid, , Spain, 28041

Sponsors and Collaborators

Adaptimmune

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02989064
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Adaptimmune:

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

Additional relevant MeSH terms:

Carcinoma

Melanoma

Head and Neck Neoplasms

Carcinoma, Transitional Cell

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on November 12, 2020