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Malignant Solid NeoplasmPhase 2NCT03610490

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

A Phase 2 study testing Autologous Tumor Infiltrating Lymphocytes MDA-TIL, Cyclophosphamide and Fludarabine in people with Malignant Solid Neoplasm and Metastatic Colorectal Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Autologous Tumor Infiltrating Lymphocytes MDA-TIL, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
16 Oct 2018to 21 Aug 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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
  • Subjects must also have a negative dobutamine stress echocardiogram before beginning treatment
  • Subjects of childbearing potential must be willing to practice an approved highly effective method of birth control starting at the time of informed consent and for 1 year after the completion of the lymphodepletion regimen. Approved methods of birth control are as follows: hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation or hysterectomy; subject/partner status post vasectomy; implantable or injectable contraceptives; and condoms plus spermicide
  • Able to adhere to the study visit schedule and other protocol requirements
  • Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1 greater than 65% predicted or forced vital capacity (FVC) greater than 65% of predicted
  • Ovarian cancer cohort only: Subjects must have high grade non-mucinous histology (carcinosarcomas are allowed)
  • Ovarian cancer cohort only: Subjects must have failed at least two prior lines of chemotherapy (i.e. frontline adjuvant chemotherapy plus one additional line for recurrent/progressive disease), or have platinum resistant disease
  • Colorectal cohort only: Subjects with colorectal adenocarcinoma must have metastatic disease that is considered incurable with currently available therapies and have derived maximal benefit from or have become refractory to frontline conventional therapy (e.g. leucovorin calcium [calcium folinate], 5-fluorouracil and oxaliplatin [FOLFOX], leucovorin calcium, 5-fluorouracil, and irinotecan [FOLFIRI]).
  • Colorectal cohort only: Subjects should have low disease burden such that in the treating physician's opinion the patient would not require additional intervening treatment for 7-8 weeks (required for TIL harvest and manufacturing)
  • Pancreatic adenocarcinoma cohort only: Subjects must have histologically or cytologically documented diagnosis of PDAC with oligo-metastatic disease
  • Pancreatic adenocarcinoma cohort only: Subjects must have progressed on, or received maximal benefit from, front-line therapy
  • Pancreatic adenocarcinoma cohort only: Patients may have received unlimited lines of prior standard of care therapy
  • Pancreatic adenocarcinoma cohort only: Patients with ascites or carcinomatosis are not eligible for the study
  • Pancreatic adenocarcinoma cohort only: Patients will need an albumin of >= 3.0 mg/dL within 7 days of enrollment
  • TREATMENT INCLUSION CRITERION: Within 24 h of starting lymphodepleting chemotherapy, subjects must meet the following laboratory criteria:
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Hemoglobin >= 9.0 g/dL (transfusion allowed)
  • Platelet count >= 100,000/mm3
  • ALT/SGPT and AST/SGOT =< 2.5 x the upper limit of normal (ULN)
  • Patients with liver metastases may have liver function tests (LFT) =< 5.0 x ULN
  • Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min
  • Total bilirubin =< 1.5 X ULN

Who cannot join

  • 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
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  • 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
  • Patients who have a contraindication to or history of hypersensitivity reaction to any components or excipients of the TIL therapy or the other study drugs: NMA-LD (cyclophosphamide, mesna, and fludarabine); IL-2; any component of the TIL infusion product formulation including human serum albumin (HSA), IL-2, and dextran-40
  • Any other condition that in the investigator's judgement would significantly increase the risks of participation
  • Patient has any complication or delayed healing from excisional procedure that in the investigator's opinion would increase the risks of lymphodepletion, adoptive TIL therapy and adjuvant IL-2
  • Patients has a decline in performance status to ECOG > 1 (at the visit prior to admission for lymphodepletion)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Clinical Study to Assess Efficacy and Safety of MDA-TIL (Autologous Expanded Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate efficacy using objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in subjects with ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), and colorectal cancers.

SECONDARY OBJECTIVES:

  1. Determine the disease control rate (DCR) within and across cohorts. II. Determine the duration of response (DOR). III. Determine progression-free survival (PFS) and overall survival (OS). IV. Further characterize the safety profile of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) across multiple tumor types.

EXPLORATORY OBJECTIVES:

  1. Establish duration of TIL persistence. II. Compare the molecular and immunological features of tumors before and after TIL therapy.

III. Prospectively evaluate the existing immunotherapy response criteria (immune-related Response Evaluation Criteria in Solid Tumors [irRECIST]) as the best response assessment tool for TIL therapy among a diverse group of solid tumors.

IV. Investigate TIL attributes (CD8 %, CD27 and CD28 expression) and correlation with response to therapy.

  1. Assess tumor marker (CA19-9; CA-125) response in patients who produce this tumor marker.

VI. Assess Health-Related Quality of Life (HRQOL).

OUTLINE:

LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide intravenously (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.

After completion of study treatment, patients are followed up at week 18, at 6, 9, 12, 18, and 24 months, and then every 3 months for up to 3 years.

Being tested
Autologous Tumor Infiltrating Lymphocytes MDA-TIL, Cyclophosphamide, Fludarabine, Interleukin-2, Quality-of-Life Assessment
Medical subject headings
Ovarian Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Tumor Infiltrating Lymphocytes MDA-TILBiological

    Also called MDA Autologous TILs, MDA Autologous Tumor Infiltrating Lymphocytes, MDA-TILs

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Interleukin-2Biological

    Also called Epidermal Thymocyte Activating Factor, ETAF, IL-2, IL2

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

Study groups in NCT03610490
Study groupRoleWhat they receive
Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)ExperimentalLYMPHODEPLETION 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.
Receives: Biological: Autologous Tumor Infiltrating Lymphocytes MDA-TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Interleukin-2; Other: Quality-of-Life Assessment

What is being measured

The primary outcome is the main question the study is designed to answer.

  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%.

    Measured: Through 4 years

Secondary outcomes (2)

  1. Number of Participants With Stable Disease

    Participants will be evaluated at 6 and 12 weeks for response.

    Measured: 6 weeks, 12 weeks

  2. Progression-free Survival (PFS) and Overall Survival (OS)

    Measured: 44.8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Aug 2018
  2. Study start16 Oct 2018
  3. Primary completion21 Aug 2024
  4. Study completion21 Aug 2024

Why it stopped: Lack of Efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03610490
Sponsor's protocol ID
2017-0671
Other IDs
NCI-2018-01509, 2017-0671
Status last verified
Apr 2025
First submitted
24 Jul 2018
Last updated
17 Apr 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38309721

  • 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.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Autologous Tumor Infiltrating Lymphocytes MDA-TIL, Cyclophosphamide and Fludarabine in people with Malignant Solid Neoplasm and Metastatic Colorectal Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Through 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03610490, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025; AzTrials last refreshed its copy on 7 Nov 2026.

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