Adoptive Cell Therapy Across Cancer Diagnoses

NCT03296137 | Completed Phase 1 Results DMC

• 1 other identifier: AA1720
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will perform tumor-infiltrating lymphocyte (TIL)-based adoptive T-cell therapy in combination with checkpoint inhibition on cancer patients across all cancer diagnoses.

Conditions

Cancer

Keywords

immune therapy; TILs; Adoptive cell therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants and Type of Reported Adverse Events

  Determine the safety of the administration of TIL therapy including checkpoint inhibitors, lymphodepleting chemotherapy and Interleukin-2 for patients with cancer by reporting grade \>2 adverse events according to CTCAE v. 4.0

  Up to 2,5 years from begin of study

Secondary Outcomes (3)

• Time to Disease Progression

  Until study completion

• Overall Survival

  Until study completion

• Overall Response Rate

  The patients were evaluated every 6-12 weeks (median 90 days) and after therapy and until study completion (max 220 days).

Study Arms (1)

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

EXPERIMENTAL

Biological: Autologous tumor-infiltrating lymphocytes; Drug: Ipilimumab; Drug: Nivolumab; Drug: proleukin; Drug: Cyclophosphamide; Drug: Fludara

Interventions

Autologous tumor-infiltrating lymphocytes BIOLOGICAL

Tumor-infiltrating lymphocytes grown ex-vivo from resected from cancer tissue and reapplied to the patient via an intravenous infusion.

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

Ipilimumab DRUG

One treatment with ipilimumab (3 mg/kg) prior to tumor resection.

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

Nivolumab DRUG

4 doses of nivolumab. Starting 2 days prior to TIL infusion and every 2 weeks hereafter.

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

proleukin DRUG

2 MIE s.c. injection, after TIL infusion and continuing for 2 weeks

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

Cyclophosphamide DRUG

2 doses (60 mg/kg) prior to TIL infusion

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

Fludara DRUG

5 doses (25 mg/m2) prior to TIL infusion

Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically verified metastatic or locally advanced cancer diagnosis
• At least one lesion (\>1 cm3) available for surgical resection
• Not candidate for standard treatment options
• Age of 18-70 years
• Performance status of 1 or 0.
• Life expectancy \> 6 months
• One or more measurable parameter according to RECIST 1.1.
• No significant toxicity from previous cancer treatments (CTC≤1). Except alopecia (CTC≤2) or neuropathy (CTC≤2)
• Sufficient organ function, including:
• Absolute neutrophil count (ANC) ≥ 1.500 /µl
• Leucocyte count ≥ normal limit
• Platelets ≥ 100.000 /µl and \<700.000 /µl
• Hemoglobin ≥ 6,0 mmol/l (regardless of prior transfusion)
• S-creatinine \< 140
• S-bilirubin ≤ 1,5 times upper normal limit

You may not qualify if:

• A history of prior malignancies. Patients treated for another malignancy can only participate if they are without signs of disease for a minimum of 3 years after last treatment.
• Primary brain tumor or verified brain metastases
• Known hypersensitivity to one of the active drugs or excipients.
• Significant medical conditions, including but not limited to severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus.
• Creatinine clearance below 70 ml/min .
• Acute or chronic infections with HIV, hepatitis, syphilis etc.
• Severe allergies or previous anaphylactic reactions.
• Active autoimmune disease, such as autoimmune neutropenia/thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, Sjögren's syndrome, sclerodermia, myasthenia gravis, goodpastures disease, addison's disease, hashimoto's thyroiditis, graves' disease etc.
• Pregnant women and women who are breastfeeding.
• Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone methotrexate etc.)
• Simultaneous treatment with other experimental drugs.
• Simultaneous treatment with other systemic anti-cancer treatments.
• Patients with active or uncontrollable hypercalcemia.

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (1)

Center for Cancer immune Therapy (CCIT), Dept. of Hematology and dept. of Oncology

Copenhagen, 2730, Denmark

Location

Related Publications (1)

• Kverneland AH, Chamberlain CA, Borch TH, Nielsen M, Mork SK, Kjeldsen JW, Lorentzen CL, Jorgensen LP, Riis LB, Yde CW, Met O, Donia M, Svane IM. Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types. J Immunother Cancer. 2021 Oct;9(10):e003499. doi: 10.1136/jitc-2021-003499.

  PMID: 34607899 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Ipilimumab; Nivolumab; aldesleukin; Cyclophosphamide; fludarabine phosphate

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Anders Kverneland, MD, PhD
• Organization: National Center for Cancer Immune Therapy, Herlev Hospital

anders.kverneland@regionh.dk

+4538686467

Study Officials

• Anders H Kverneland, MD

  Center for Cancer Immune Therapy, Herlev Hospital

  PRINCIPAL INVESTIGATOR

• Inge Marie Svane, MD, Prof.

  Center for Cancer Immune Therapy, Herlev Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D. Professor

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 28, 2017
• Study Start: October 13, 2017
• Primary Completion: March 13, 2020
• Study Completion: July 1, 2020
• Last Updated: October 26, 2024
• Results First Posted: October 26, 2024

Record last verified: 2024-10

Locations

DK (1)