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Trial record 5 of 283 for:    Tumor infiltrating lymphocytes

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

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ClinicalTrials.gov Identifier: NCT03610490
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : March 22, 2019
Sponsor:
Collaborators:
Iovance Biotherapeutics, Inc.
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well autologous tumor infiltrating lymphocytes MDA-TIL works in treating patients with ovarian cancer, osteosarcoma, or pancreatic ductal adenocarcinoma that has come back or does not respond to treatment. 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.

Condition or disease Intervention/treatment Phase
High Grade Ovarian Serous Adenocarcinoma Oligometastasis Ovarian Carcinosarcoma Pancreatic Ductal Adenocarcinoma Recurrent Osteosarcoma Recurrent Ovarian Carcinoma Refractory Osteosarcoma Refractory Ovarian Carcinoma Biological: Autologous Tumor Infiltrating Lymphocytes MDA-TIL Drug: Cyclophosphamide Drug: Fludarabine Biological: Interleukin-2 Other: Quality-of-Life Assessment Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. 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 osteosarcoma.

SECONDARY OBJECTIVES:

I. 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:

I. 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 (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.

V. 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 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Study to Assess Efficacy and Safety of MDA-TIL (Autologous Expanded Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types
Actual Study Start Date : August 17, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2021


Arm Intervention/treatment
Experimental: Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, and fludarabine IV over 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
Given IV
Other Names:
  • MDA Autologous TILs (SY)
  • MDA-TILs (CN); MDA Autologous Tumor Infiltrating Lymphocytes (SY);

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Biological: Interleukin-2
Given IV
Other Names:
  • 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

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. Objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria [ Time Frame: Up to 5 years ]
    ORR will use 80% confidence interval by the Wilson score method.


Secondary Outcome Measures :
  1. Complete response rate (CRR) as measured by RECIST 1.1 criteria [ Time Frame: Up to 5 years ]
    CRR will adopt the 2-sided 95% criteria.

  2. Disease control rate (DCR) as measured by RECIST 1.1 criteria [ Time Frame: Up to 5 years ]
    DCR will adopt the 2-sided 95% criteria. DCR includes complete response, partial response, and stable disease.

  3. Duration of response (DOR) as measured by RECIST 1.1 criteria [ Time Frame: Up to 5 years ]
    DOR will adopt the 2-sided 95% criteria.

  4. Progression-free survival (PFS) as measured by RECIST 1.1 criteria [ Time Frame: At 6 and 12 months ]
    PFS will be summarized using Kaplan-Meier estimates.

  5. Overall survival (OS) [ Time Frame: At 6 and 12 months ]
    OS will be summarized using Kaplan-Meier estimates.

  6. Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [ Time Frame: Up to 5 years ]
    Safety endpoints will include overall assessment of adverse events (AEs) including grade 3 or greater non-hematological toxicities, serious adverse events and treatment-emergent AEs by grade and relationship to the study treatment.


Other Outcome Measures:
  1. Duration of tumor infiltrating lymphocyte (TIL) persistence [ Time Frame: Up to 5 years ]
    Duration of TIL persistence is determined by T cell receptor (TCR) sequencing of infused T cells serially isolated following MDA-TIL infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs. A paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy. Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

  2. Response as determined by the immune-related response criteria [ Time Frame: Up to 5 years ]
    A paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy. Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

  3. Assessment of immunological phenotype of autologous tumor infiltrating lymphocytes MDA-TIL [ Time Frame: At the time of infusion ]
    A paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy. Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

  4. Tumor assessment as determined by immunohistochemistry, TCR sequencing, and transcriptional analysis [ Time Frame: Up to 5 years ]
    A paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy. Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.

  5. Health-related quality of life as assessed by European Organization for Research and Treatment of Cancer core 30 quality of life questionnaire [ Time Frame: Up to 5 years ]
    A paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy. Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 %, CD27 and CD28 expression, etc.) and response to therapy.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 and 70 (subjects aged 16 - 70 may be enrolled into the osteosarcoma cohort)
  • Subjects must be willing and able to provide informed consent. For patients < 18 years of age, their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
  • 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 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 and with 24 hours of starting lymphodepleting chemotherapy)
  • Hemoglobin >= 9.0 g/dL (transfusion allowed) (within 7 days of enrollment and with 24 hours of starting lymphodepleting chemotherapy)
  • Platelet count >= 100,000/mm^3 (within 7 days of enrollment and with 24 hours of starting lymphodepleting chemotherapy)
  • 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 and with 24 hours of starting lymphodepleting chemotherapy)
  • Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min (within 7 days of enrollment and with 24 hours of starting lymphodepleting chemotherapy)
  • Total bilirubin =< 1.5 x ULN (within 7 days of enrollment and with 24 hours of starting lymphodepleting chemotherapy)
  • 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 and with 24 hours of starting lymphodepleting chemotherapy)
  • Negative serum pregnancy test (female subjects of childbearing potential) (within 7 days of enrollment and with 24 hours of starting lymphodepleting chemotherapy)
  • 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 40 years of age and older must also have a negative stress cardiac test (i.e. EKG stress test, stress thallium, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia). Stress test may be required of subjects less than 40 years of age if warranted by family history or risk factors by the treating investigator
  • 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)
  • Osteosarcoma cohort only: Subjects with osteosarcomas must have relapsed or become refractory to conventional therapy and have received a regimen including some combination of high-dose methotrexate, doxorubicin, cisplatin, and/or ifosfamide
  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03610490


Contacts
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Contact: Amir Jazaeri 713-792-8578 aajazaeri@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Ljiljana Milojevic    713-792-8578    lmilojev@mdanderson.org   
Principal Investigator: Amir A. Jazaeri         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Iovance Biotherapeutics, Inc.
Bristol-Myers Squibb
Investigators
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Principal Investigator: Amir Jazaeri M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03610490     History of Changes
Other Study ID Numbers: 2017-0671
NCI-2018-01509 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0671 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: March 22, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Ovarian Neoplasms
Mixed Tumor, Mullerian
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms, Complex and Mixed
Carcinoma
Adenocarcinoma
Osteosarcoma
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Carcinosarcoma
Sarcoma
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Cystadenocarcinoma
Cyclophosphamide
Fludarabine phosphate
Fludarabine