CT Antigen TCR-Engineered T Cells for Myeloma

NCT01892293 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: ADP-0011-002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

This study will enroll patients with multiple myeloma who have received prior therapy for their disease but their disease has progressed or relapsed.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Autologous stem cell transplantation; Received initial treatment previously

Outcome Measures

Primary Outcomes (1)

• Adverse Events Related to Study Treatment

  Number of Participants with NCI CTCAE Version 4.0 Adverse Events related to study treatment greater than or equal to Grade 3

  Up to 12 months

Secondary Outcomes (2)

• Evaluate the Direct Anti-tumor Activity of NY-ESO-1ᶜ²⁵⁹T

  180 days

• Peak Persistence of Modified T-cells in the Peripheral Blood

  Days 1, 3, 5, 8, 15, 22, 29, 43, 101, 130 181, every 3 months thereafter

Study Arms (1)

Autologous genetically modified T cells

EXPERIMENTAL

Patients with a confirmed diagnosis of myeloma, with measurable disease, and who have received prior therapy for their myeloma that includes an IMiDs and a proteasome inhibitor and who have relapsed or progressive disease, will receive treatment with NY-ESO-1c259-modified T cells. An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to \< 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range.

Drug: Treatment with NY-ESO-1c259-modified T cells

Interventions

Treatment with NY-ESO-1c259-modified T cells DRUG

An intended total dose of ≥0.1-1e10 total cells will be administered as a single infusion. A low dose infusion of 1e8 to \< 1e9 will be allowed for patients if cells do not expand sufficiently to reach the target dose range. For patients whose disease progresses and whose tumor still expresses tumor antigen and HLA-A201, a second infusion of up to 5e10 cells may be given.

Autologous genetically modified T cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Written informed consent must be obtained from all patients before entry into the study
• \. Patients must have a diagnosis of myeloma (see Appendix A for diagnostic criteria).
• \. Patients must have progressive or active disease following prior therapy for their myeloma which:
• includes an IMiD and proteasome inhibitor as separate lines or a combined line of therapy
• May include prior auto-SCT but not prior allo-SCT
• Patients who have failed second or third line therapy and beyond, such as DPACE, and who are experiencing a partial response rather than progressive disease are also eligible.
• \. Patients must have measurable disease on study entry. Measurable disease may include quantifiable or detectable levels of serum or urine paraprotein. For patients with minimally secretory disease on study entry, serum free kappa or lambda light chain levels, or the serum free light chain ratio may be measured and used for disease monitoring if abnormal.
• \. Patients must be HLA-A201 as determined by a CLIA certified (or equivalent) clinical laboratory. (This determination will be made under a pre-enrollment screening ICF)
• \. Patients must have confirmed expression of NY-ESO-1 and/or LAGE-1 by RT-PCR, immunohistochemistry or quantigene analysis. (This determination will be made under a pre-enrollment screening ICF)

You may not qualify if:

• \. Pregnant or nursing females 2. HIV or HTLV-1/2 seropositivity 3. Known history of myelodysplasia 4. Known history of chronic active hepatitis or liver cirrhosis (if suspected by laboratory studies, should be confirmed by liver biopsy).
• \. Active Infection with HBV or HCV
• Active hepatitis B infection as determined by test for hepatitis B surface antigen.
• Active hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV RNA by any RT PCR or bDNA assay must be performed at screening by a local laboratory with a CLIA certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.
• \. Prior allogeneic transplant 7. History of severe autoimmune disease requiring steroids or other immunosuppressive treatments.
• \. Active immune-mediated diseases including: connective tissue diseases, uveitis, sarcoidosis, inflammatory bowel disease, multiple sclerosis.
• \. Evidence or history of other significant cardiac, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease which would likely increase the risks of participating in the study. The specific type of stress test will be selected at the PI's discretion.
• \. Active bacterial or systemic viral or fungal infections.

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (2)

City of Hope

Duarte, California, 91010, United States

Location

Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Clinical Trials Management
• Organization: Adaptimmune

clinicaltrials@adaptimmune.com

Study Officials

• Edward Stadtmauer, MD

  University of Pennsylvania

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2013
• First Posted: July 4, 2013
• Study Start: October 15, 2013
• Primary Completion: December 10, 2014
• Study Completion: April 9, 2018
• Last Updated: January 10, 2019
• Results First Posted: July 24, 2018

Record last verified: 2019-01

Locations

US (2)