A First-In-Human Phase 1 Trial of T-Cell Membrane-Anchored Tumor Targeted Il12 (Attil12)- T-Cell Therapy in Subjects With Advanced/Metastatic Soft Tissue and Bone Sarcoma

NCT05621668 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2021-0619NCI-2022-09675
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

To find a recommended dose of attIL2-T cell therapy that can be given to patients with soft tissue or bone sarcomas and to see if it can help to control the disease.

Conditions

Soft Tissue Sarcoma; Bone Sarcoma

Outcome Measures

Primary Outcomes (1)

• To examine the incidence of adverse events.

  National Cancer Institute, Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. from screening through the treatment period

  through study completion; an average of 1 year.

Study Arms (2)

Part A: Dose Findings (MTD)

EXPERIMENTAL

The dose of attIL2-T cell therapy the participants will receive will depend on when the participants joined this study. The first group of participants will receive the lowest dose level of attIL2-T cell therapy.

Drug: Cyclophosphamide; Drug: attIL2-T cells

Part B: Osteosarcoma Dose Expansion

EXPERIMENTAL

Participants will receive attIL2-T cell therapy at the recommended dose that was found in Phase 1.

Drug: Cyclophosphamide; Drug: attIL2-T cells

Interventions

attIL2-T cells DRUG

Given by IV (vein)

Part A: Dose Findings (MTD); Part B: Osteosarcoma Dose Expansion

Cyclophosphamide DRUG

Given by IV (vein)

Also known as: Cytoxan®, Neosar®

Part A: Dose Findings (MTD); Part B: Osteosarcoma Dose Expansion

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age .12 years old
• Histologically-confirmed locally advanced or metastatic soft tissue or bone sarcoma
• Osteosarcoma expansion cohort: histologically confirmed unresectable recurrent/metastatic osteosarcoma
• Evaluable disease.
• Patients must have received at least 1 prior line of systemic therapy for the treatment of sarcoma, unless no standard therapy exists for a specific sarcoma subtype
• Prior Cancer Therapy . At least 3 weeks must have elapsed since the last cytotoxic chemotherapy or immunotherapy prior to leukapheresis/PBMC collection.
• For targeted therapies, at least 4 half-lives or 3 weeks must have elapsed prior to leukapheresis (whichever is shorter).
• Standard of care anti-cancer therapy will be permitted following leukapheresis but prior to initiation of cyclophosphamide such that:
• At least 3 weeks must have elapsed since last cytotoxic chemotherapy or immunotherapy prior to starting treatment with cyclophosphamide.
• For targeted therapies, at least 4 half-lives or 3 weeks must have elapsed prior to initiation of treatment with cyclophosphamide (whichever is shorter).
• At least 2 weeks must have elapsed since last radiation therapy prior to cyclophosphamide.
• Investigational anti-cancer therapy will not be permitted.
• ECOG performance status of 0 or 1 (Performance level as measured by Karnofsky for patients . 16 years of age or Lansky for patients \< 16 years of age, see Appendix B)
• Participants must be willing to undergo tumor biopsy
• Patients in whom biopsy is medically contraindicated or otherwise high risk will not be excluded and may forego research tumor biopsies

You may not qualify if:

• Known sensitivity to cyclophosphamide and/or study agents Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Subjects previously treated central nervous system metastases that are radiographically and neurologically stable for at least 6 weeks and do not require corticosteroids (of any dose) for symptomatic management for at least 14 days prior to first dose of attIL12-T cells are permitted to enroll. 3. Presence of metastatic disease in or near vital or critical structures that in the judgement of the treating physician in communication with PI or their delegate may lead to concern of immediate risk for harm from the inflammatory response.
• \. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment at the time of leukapheresis or attIL12 T cell infusion.
• Standard of care anti-cancer therapy will be permitted following leukapheresis and prior to initiation of cyclophosphamide as bridging therapy (per section 12.4.1).
• Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• In addition, local treatment (eg, by local surgery, radiotherapy, or ablation) of isolated lesions for palliative intent is acceptable beyond 30 days following attIL12 T cell administration with prior consultation and in agreement with the PI.
• Investigational therapy for supportive care (e.g. COVID vaccine) will be permitted, as long as it is reviewed and discussed with the PI.
• \. History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
• \. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products 7. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of treatment or if still recovering from prior surgery. Biopsy as per study protocol is allowed 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs from the study agents, or compromise the ability of the subject to give written informed consent.
• \. Subjects with cognitive impairment, including adults with cognitive impairment such as trisomy 21 or similar conditions are not specifically excluded from participation, such that appropriate written informed consent is obtained from the parent or legal guardian and they are able to complete with the study protocol requirements and treatment.
• \. Active concurrent second malignancy 11. Pregnant or lactating women 12. Any positive test result for hepatitis B or C virus indicating acute or chronic infection 13. Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• John Livingston, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Livingston, MD

CONTACT

(713) 792-3626; jalivingston@mdanderson.org

Study Design

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

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: September 8, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)