Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma

NCT03610490 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2017-0671NCI-2018-01509
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well autologous tumor infiltrating lymphocytes MDA-TIL works in treating patients with ovarian cancer, colorectal cancer, or pancreatic ductal adenocarcinoma that has come back (recurrent) or does not respond to treatment (refractory). Autologous tumor infiltrating lymphocytes MDA-TIL, made by collecting and growing specialized white blood cells (called T-cells) from a patient's tumor, may help to stimulate the immune system in different ways to stop tumor cells from growing.

Conditions

Malignant Solid Neoplasm; Metastatic Colorectal Adenocarcinoma; Metastatic Ovarian Carcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Platinum-Resistant Ovarian Carcinoma; Recurrent High Grade Ovarian Serous Adenocarcinoma; Recurrent Ovarian Carcinosarcoma; Refractory Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in Participants With Ovarian Cancer (OVCA), PDAC (Pancreatic Cancer), and Colorectal Cancers (CRC) According to RECIST v1.1 in Subjects With Ovarian Cancer (OVCA), PDAC (Pancreatic Cancer), and Colorectal Cancers (CRC)

  The ORR is derived as the sum of the number of patients with a confirmed CR or partial response (PR) divided by the number of patients in the All-Treated analysis set x 100%.

  Through 4 years

Secondary Outcomes (2)

• Number of Participants With Stable Disease

  6 weeks, 12 weeks

• Progression-free Survival (PFS) and Overall Survival (OS)

  44.8 months

Study Arms (1)

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

EXPERIMENTAL

LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, and fludarabine IV over 15-30 minutes on days -5 to -1 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autologous tumor infiltrating lymphocytes MDA-TIL IV over 45 minutes on day 0. Patients then receive IL-2 IV over 30 minutes on days 1-4 for up to 6 doses in the absence of disease progression or unacceptable toxicity.

Biological: Autologous Tumor Infiltrating Lymphocytes MDA-TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Interleukin-2; Other: Quality-of-Life Assessment

Interventions

Autologous Tumor Infiltrating Lymphocytes MDA-TIL BIOLOGICAL

Given IV

Also known as: MDA Autologous TILs, MDA Autologous Tumor Infiltrating Lymphocytes, MDA-TILs

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

Interleukin-2 BIOLOGICAL

Given IV

Also known as: Epidermal Thymocyte Activating Factor, ETAF, IL-2, IL2, IL2 Protein, Interleukin 2, Interleukin 2 Precursor, Interleukin II, Lymphocyte Mitogenic Factor, Mitogenic Factor, Ro-236019, T Cell Growth Factor, T-Cell Growth Factor, TCGF, Thymocyte Stimulating Factor, TSF

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

Eligibility Criteria

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

You may qualify if:

• Subjects must be willing and able to provide informed consent
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 at enrollment and within 7 days of initiating lymphodepleting chemotherapy
• Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed) for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment
• Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior to tumor resection for preparing TIL therapy
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (within 7 days of enrollment)
• Hemoglobin \>= 9.0 g/dL (transfusion allowed) (within 7 days of enrollment)
• Platelet count \>= 100,000/mm\^3 (within 7 days of enrollment)
• Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \< 2.5 x the upper limit of normal (ULN)
• Patients with liver metastases may have liver function test \[LFT\] =\< 5.0 x ULN (within 7 days of enrollment)
• Calculated creatinine clearance (Cockcroft-Gault) \>= 50.0 mL/min (within 7 days of enrollment)
• Total bilirubin =\< 1.5 x ULN (within 7 days of enrollment)
• Prothrombin time (PT) \& activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (correction with vitamin K allowed) unless subject is receiving anticoagulant therapy (which should be managed according to institutional norms prior to and after excisional biopsy) (within 7 days of enrollment)
• Negative serum pregnancy test (female subjects of childbearing potential) (within 7 days of enrollment)
• Subjects must not have a confirmed human immunodeficiency virus (HIV) infection
• Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms

You may not qualify if:

• Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system. Principal investigator (PI) or his/her designee shall make the final determination regarding appropriateness of enrollment
• Patients with active viral hepatitis
• Patients who have a left ventricular ejection fraction (LVEF) \< 45% at screening
• Patients with a history of prior adoptive cell therapies
• Persistent prior therapy-related toxicities greater than grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) v. 4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment
• Primary immunodeficiency
• History of organ or hematopoietic stem cell transplant
• Chronic steroid therapy, however prednisone or its equivalent is allowed at \< 10 mg/day
• Patients who are pregnant or nursing
• Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his/her designee, would prevent adequate informed consent
• History of clinically significant autoimmune disease including active, known, or suspected autoimmune disease. Subjects with resolved side effects from prior checkpoint inhibitor therapy, vitiligo, psoriasis, type 1 diabetes or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded
• History of clinically significant chronic obstructive pulmonary disease (COPD), asthma, or other chronic lung disease
• History of a second malignancy (diagnosed in the last 5 years). Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• History of known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to initiation of lymphodepletion
• Has received a live vaccine within 30 days prior to the initiation of lymphodepletion

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• Iovance Biotherapeutics: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Amaria R, Knisely A, Vining D, Kopetz S, Overman MJ, Javle M, Antonoff MB, Tzeng CD, Wolff RA, Pant S, Lito K, Rangel K, Fellman B, Yuan Y, Lu KH, Sakellariou-Thompson D, Haymaker CL, Forget MA, Hwu P, Bernatchez C, Jazaeri AA. Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. J Immunother Cancer. 2024 Feb 2;12(2):e006822. doi: 10.1136/jitc-2023-006822.

  PMID: 38309721 DERIVED

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Ovarian Neoplasms; Colorectal Neoplasms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2; 4-toluenesulfonyl fluoride

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Amir A Jazaeri, MD
• Organization: M D Anderson Cancer Center

aajazaeri@mdanderson.org

713-792-8578

Study Officials

• Amir A Jazaeri

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2018
• First Posted: August 1, 2018
• Study Start: October 16, 2018
• Primary Completion: August 21, 2024
• Study Completion: August 21, 2024
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-04

Locations

US (1)