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LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

Primary Purpose

Bone Sarcoma, Dedifferentiated Chondrosarcoma, Giant Cell Tumor of Bone

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aldesleukin
Autologous Tumor Infiltrating Lymphocytes LN-145
Autologous Tumor Infiltrating Lymphocytes LN-145-S1
Cyclophosphamide
Fludarabine
Ipilimumab
Nivolumab
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bone Sarcoma

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.
  • Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed as detailed in protocol) 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 enrollment for preparing TIL therapy. Palliative therapy may be received during the screening period with principal investigator (PI) approval for lesions that are not expected to be used for TIL generation or as target lesions.
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days of enrollment).
  • Hemoglobin >= 8.0 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 tests (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. If neither of these tests can be performed, subject may complete alternative cardiac evaluation deemed clinically appropriate based on the recommendation of cardiology.
  • 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.
    • 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), and have platinum resistant disease.
  • TIL-ICI ovarian cancer cohort only: Same as "ovarian cancer" above.
  • TIL-ICI ovarian cancer cohort only: Enrolled after activation of protocol version 2.0.
  • 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.
  • Other bone and soft tissue sarcomas cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed.
  • Other bone and soft tissue sarcomas cohort only: Subjects with other soft tissue sarcomas who have received at least one line of therapy.
  • TIL-ICI sarcoma 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.
  • TIL-ICI sarcoma cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed.
  • TIL-ICI sarcoma cohort only: Subjects with other soft tissue sarcomas who have received at least one line of therapy.
  • TIL-ICI sarcoma cohort only: Enrolled after activation of protocol version 2.0.
  • Anaplastic and poorly-differentiated thyroid cancer cohort only: Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include consistent with, or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma.
  • Anaplastic and poorly-differentiated thyroid cancer cohort only: Measurable distant metastatic disease by RECIST v1.1.
  • Anaplastic and poorly-differentiated thyroid cancer cohort only: Subjects who are planned for surgical resection of their tumor, or subjects who are planned for surgery to stabilize the airway (i.e., tracheostomy). Subjects who have a stable airway at the time of consent are eligible if there is tumor that can be resected for TIL manufacturing.
  • Anaplastic and poorly-differentiated thyroid cancer cohort only: Previous external beam radiation to the neck is allowed as long as there is a measurable lesion that can be biopsied (separate from the area of radiated tumor) and at least one other for RECIST response assessment.
  • TIL-ICI-TNBC cohort only: Subjects must have a confirmed diagnosis of metastatic triple negative breast cancer (Stage IV or recurrent) histologically confirmed as per the AJCC staging system.
  • Subjects must have TNBC, defined from standard pathologic assays as negative for ER and PR (<10% tumor staining) and negative for HER2 (IHC<3, gene copy number not amplified; per ASCO/CAP guidelines).
  • Subjects must have had at least 1 and no more than 3 prior lines of systemic anticancer therapy for metastatic disease.
  • The resectable lesion must be a minimum of 1.5 cm in diameter.

Exclusion Criteria:

  • Active or uncontrolled intercurrent illness, including but not limited to ongoing or active infections, 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) version (v)4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment.

    • Patients who have had a documented grade 2 or greater diarrhea or colitis due to previous immunotherapy must have been asymptomatic for at least 6 months or had a normal colonoscopy post checkpoint treatment, by visual assessment, prior to enrollment.
    • Patients with immunotherapy-related endocrinopathies (e.g. hypothyroidism or hypopituitarism, who are stable on hormonal substitution) and controlled with hormonal replacement, are allowed.
  • 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, interstitial lung disease, 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. For the thyroid cancer cohort, subjects have a higher likelihood of prior cancers. Therefore, for this cohort, history of prior thyroid cancer or other indolent cancers is not considered exclusionary if in the opinion of the treating physician such cancers are indolent or unlikely to affect the overall prognosis based on the active thyroid cancer.
  • 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: non-myeloablative-lymphodepletion (NMA-LD) (cyclophosphamide, mesna, and fludarabine); IL-2; antibiotics of the aminoglycoside group (i.e., streptomycin, gentamicin); any component of the TIL infusion product formulation including human serum albumin (HSA), IL-2, and dextran-40, nivolumab or ipilimumab.
  • Any other condition that in the investigator's judgement would significantly increase the risks of participation.

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ICI Ovarian Cancer, Sarcomas, Triple Negative Breast Cancer (LN-145-S1, nivolumab)

Thyroid Cohort (LN-145)

Arm Description

Ipilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.

Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.

Outcomes

Primary Outcome Measures

Objective response rate
Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.

Secondary Outcome Measures

Disease control rate
Duration of response
Progression free survival
Will be summarized using Kaplan-Meier estimates.
Overall survival
Will be summarized using Kaplan-Meier estimates.
Incidence of adverse events of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types

Full Information

First Posted
February 22, 2018
Last Updated
October 2, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Iovance Biotherapeutics, Inc., National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03449108
Brief Title
LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas
Official Title
Clinical Study to Assess Efficacy and Safety of LN-145/LN-145-S1 (Autologous Centrally Manufactured Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 27, 2018 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Iovance Biotherapeutics, Inc., National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well autologous tumor infiltrating lymphocytes LN-145 (LN-145) or LN-145-S1 works in treating patients with ovarian cancer, triple negative breast cancer (TNBC), anaplastic thyroid cancer, osteosarcoma, or other bone and soft tissue sarcomas that do not respond to treatment (refractory) or that has come back (relapsed). LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from the patient's tumor. LN-145-S1 is made using a modified process that chooses a specific portion of the T-cells. The T cells may specifically recognize, target, and kill the tumor cells.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate efficacy using objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in each cohort. 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 with tumor infiltrating lymphocytes (TIL) across multiple tumor types. EXPLORATORY OBJECTIVES: I. Establish duration of tumor-infiltrating lymphocyte (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 [ir]RECIST) as the best response assessment tool for TIL therapy among a diverse group of solid tumors. IV. To investigate TIL attributes (CD8 percentage [%], CD27 and CD28 expression) and correlation with response to therapy. V. Assess tumor marker (CA-125) response in patients who produce this tumor marker. VI. To assess Health-Related Quality of Life (HRQOL). OUTLINE: Patients are assigned to 1 of 2 cohorts. THYROID CANCER COHORT: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. ICI OVARIAN CANCER, OSTEOSARCOMA, Triple Negative Breast Cancer, or OTHER BONE AND SOFT TISSUE SARCOMAS COHORT: Within 2-4 weeks prior to surgery, patients receive a single dose of nivolumab IV over 30 minutes, followed by a single dose of ipilimumab IV over 30 minutes Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. For cohorts treated without immune checkpoint inhibitors, completion of treatment is defined as having received any volume of LN-145/LN-145-S1 infusion followed by at least 1 dose of adjuvant IL-2. For cohorts treated with TIL + ICI, completion of treatment will correspond to the last dose of nivolumab or IL2 (if the subject is deemed unsuitable to receive adjuvant nivolumab). Patients are followed up at 18 weeks, 6, 9, 12, 18 and 24 months, then every 3 months for at least 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Sarcoma, Dedifferentiated Chondrosarcoma, Giant Cell Tumor of Bone, Malignancy in Giant Cell Tumor of Bone, Malignant Solid Neoplasm, Ovarian Carcinosarcoma, Platinum-Resistant Ovarian Carcinoma, Poorly Differentiated Thyroid Gland Carcinoma, Recurrent Osteosarcoma, Recurrent Ovarian Carcinoma, Refractory Osteosarcoma, Soft Tissue Sarcoma, Thyroid Gland Anaplastic Carcinoma, Thyroid Gland Squamous Cell Carcinoma, Undifferentiated High Grade Pleomorphic Sarcoma of Bone, Triple Negative Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ICI Ovarian Cancer, Sarcomas, Triple Negative Breast Cancer (LN-145-S1, nivolumab)
Arm Type
Experimental
Arm Description
Ipilimumab will be administered as a single dose prior to tumor resection. Nivolumab will be administered once prior to tumor resection. Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, LN-145-S1 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses. Within 12 weeks after receiving LN-145-S1, patients receive nivolumab IV over 30 minutes every 4 weeks in the absence of disease progression or unacceptable toxicity. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks and continued until unacceptable toxicity, progression, or start of another cancer therapy.
Arm Title
Thyroid Cohort (LN-145)
Arm Type
Experimental
Arm Description
Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine IV over 15-30 minutes daily on days -5 to -1, autologous tumor infiltrating lymphocytes LN-145 IV over 45 minutes on day 0 and aldesleukin IV over 30 minutes on days 1-4 for up to 6 doses.
Intervention Type
Biological
Intervention Name(s)
Aldesleukin
Other Intervention Name(s)
125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Autologous Tumor Infiltrating Lymphocytes LN-145
Other Intervention Name(s)
Autologous TILs LN-145, Autologous Tumor-infiltrating Lymphocytes LN-145, LN-145, LN145
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Autologous Tumor Infiltrating Lymphocytes LN-145-S1
Other Intervention Name(s)
Autologous TILs LN-145-S1, Autologous Tumor-infiltrating Lymphocytes LN-145-S1, LN 145-S1, LN-145-S1, LN145-S1
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fluradosa
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Objective response rate
Description
Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Disease control rate
Time Frame
Up to 3 years
Title
Duration of response
Time Frame
Up to 3 years
Title
Progression free survival
Description
Will be summarized using Kaplan-Meier estimates.
Time Frame
Up to 3 years
Title
Overall survival
Description
Will be summarized using Kaplan-Meier estimates.
Time Frame
Up to 3 years
Title
Incidence of adverse events of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types
Time Frame
Up to 3 years
Other Pre-specified Outcome Measures:
Title
Duration of TIL persistence
Description
Determined by T-cell receptor (TCR) sequencing of infused T cells serially isolated following LN-145/LN-145-S1 infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs.
Time Frame
Up to 3 years
Title
Response as determined by the immune-related response criteria
Description
Pearson correlation coefficient and linear regression, when appropriate, will be used to quantify the relationship between phenotypic attributes (CD8 percentage [%], CD27 and CD28 expression, etc.) and response to therapy.
Time Frame
Up to 3 years
Title
Immunological phenotype of LN-145 by multichannel flow cytometry
Description
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.
Time Frame
Day 0
Title
Tumor assessment via immunohistochemistry, TCR sequencing, and transcriptional analysis
Description
Paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy.
Time Frame
Baseline up to 3 years
Title
Health Related Quality of Life
Description
Assessed per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire.
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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. Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed as detailed in protocol) 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 enrollment for preparing TIL therapy. Palliative therapy may be received during the screening period with principal investigator (PI) approval for lesions that are not expected to be used for TIL generation or as target lesions. Absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days of enrollment). Hemoglobin >= 8.0 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 tests (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. If neither of these tests can be performed, subject may complete alternative cardiac evaluation deemed clinically appropriate based on the recommendation of cardiology. 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. 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), and have platinum resistant disease. TIL-ICI ovarian cancer cohort only: Same as "ovarian cancer" above. TIL-ICI ovarian cancer cohort only: Enrolled after activation of protocol version 2.0. 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. Other bone and soft tissue sarcomas cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed. Other bone and soft tissue sarcomas cohort only: Subjects with other soft tissue sarcomas who have received at least one line of therapy. TIL-ICI sarcoma 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. TIL-ICI sarcoma cohort only: Subjects with dedifferentiated chondrosarcomas, dedifferentiated giant cell tumor of bone, giant cell tumor of bone, undifferentiated pleomorphic sarcoma of bone, or high-grade unclassified sarcomas of bone must have received at least one prior line of therapy unless no standard first-line therapy exists in which case enrollment as initial therapy is allowed. TIL-ICI sarcoma cohort only: Subjects with other soft tissue sarcomas who have received at least one line of therapy. TIL-ICI sarcoma cohort only: Enrolled after activation of protocol version 2.0. Anaplastic and poorly-differentiated thyroid cancer cohort only: Pathologic findings supporting the clinical impression of anaplastic thyroid carcinoma. Diagnosis may include consistent with, or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma. Anaplastic and poorly-differentiated thyroid cancer cohort only: Measurable distant metastatic disease by RECIST v1.1. Anaplastic and poorly-differentiated thyroid cancer cohort only: Subjects who are planned for surgical resection of their tumor, or subjects who are planned for surgery to stabilize the airway (i.e., tracheostomy). Subjects who have a stable airway at the time of consent are eligible if there is tumor that can be resected for TIL manufacturing. Anaplastic and poorly-differentiated thyroid cancer cohort only: Previous external beam radiation to the neck is allowed as long as there is a measurable lesion that can be biopsied (separate from the area of radiated tumor) and at least one other for RECIST response assessment. TIL-ICI-TNBC cohort only: Subjects must have a confirmed diagnosis of metastatic triple negative breast cancer (Stage IV or recurrent) histologically confirmed as per the AJCC staging system. Subjects must have TNBC, defined from standard pathologic assays as negative for ER and PR (<10% tumor staining) and negative for HER2 (IHC<3, gene copy number not amplified; per ASCO/CAP guidelines). Subjects must have had at least 1 and no more than 3 prior lines of systemic anticancer therapy for metastatic disease. The resectable lesion must be a minimum of 1.5 cm in diameter. Exclusion Criteria: Active or uncontrolled intercurrent illness, including but not limited to ongoing or active infections, 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) version (v)4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment. Patients who have had a documented grade 2 or greater diarrhea or colitis due to previous immunotherapy must have been asymptomatic for at least 6 months or had a normal colonoscopy post checkpoint treatment, by visual assessment, prior to enrollment. Patients with immunotherapy-related endocrinopathies (e.g. hypothyroidism or hypopituitarism, who are stable on hormonal substitution) and controlled with hormonal replacement, are allowed. 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, interstitial lung disease, 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. For the thyroid cancer cohort, subjects have a higher likelihood of prior cancers. Therefore, for this cohort, history of prior thyroid cancer or other indolent cancers is not considered exclusionary if in the opinion of the treating physician such cancers are indolent or unlikely to affect the overall prognosis based on the active thyroid cancer. 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: non-myeloablative-lymphodepletion (NMA-LD) (cyclophosphamide, mesna, and fludarabine); IL-2; antibiotics of the aminoglycoside group (i.e., streptomycin, gentamicin); any component of the TIL infusion product formulation including human serum albumin (HSA), IL-2, and dextran-40, nivolumab or ipilimumab. Any other condition that in the investigator's judgement would significantly increase the risks of participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amir A Jazaeri
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center

Learn more about this trial

LN-145 or LN-145-S1 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas

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