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Iovance Alliance: LN-145 Across Multiple Tumor Types

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ClinicalTrials.gov Identifier: NCT03449108
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : June 19, 2018
Sponsor:
Collaborator:
Iovance Biotherapeutics, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if LN-145 can help to control soft tissue sarcoma, osteosarcoma, or ovarian cancer that is recurrent (has come back after treatment).

LN-145 is made by collecting and growing specialized white blood cells (called T-cells) that are collected from your own tumor.

This is an investigational study. LN-145 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how LN-145 is designed to work in more detail.

Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Bone and Articular Cartilage Malignant Neoplasms of Female Genital Organs Drug: Cyclophosphamide Drug: Fludarabine Biological: LN-145 Drug: IL-2 Drug: Mesna Behavioral: Questionnaires Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Study to Assess Efficacy and Safety of LN-145 (Autologous Centrally Manufactured Tumor Infiltrating Lymphocytes) Across Multiple Tumor Types
Actual Study Start Date : April 27, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Ovarian Cancer Drug: Cyclophosphamide
60 mg/kg/day by vein over approximately 2 hours on Days -7 and -6.
Other Names:
  • Cytoxan
  • Neosar

Drug: Fludarabine
25 mg/m2 by vein daily over approximately 15-30 minutes on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Biological: LN-145
LN-145 given by vein on Day 0.

Drug: IL-2
IL-2 infusion begin 3-24 hours after completion of the LN-145 infusion. IL-2 administered at a dose of 600,000 IU/kg (based on total body weight) and administered by vein infusion at a frequency of every 8-12 hours and continued for up to a maximum of six doses or as tolerated.
Other Names:
  • Aldesleukin
  • Interleukin
  • Proleukin

Drug: Mesna
Mesna given by vein continuously on Days -7 and -6.
Other Name: Mesnex

Behavioral: Questionnaires
Questionnaires completed one time between Day -21 and Day -14, at 12 weeks, and during follow up at Months 6, 12, 24.
Other Name: Survey

Experimental: Osteosarcoma Drug: Cyclophosphamide
60 mg/kg/day by vein over approximately 2 hours on Days -7 and -6.
Other Names:
  • Cytoxan
  • Neosar

Drug: Fludarabine
25 mg/m2 by vein daily over approximately 15-30 minutes on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Biological: LN-145
LN-145 given by vein on Day 0.

Drug: IL-2
IL-2 infusion begin 3-24 hours after completion of the LN-145 infusion. IL-2 administered at a dose of 600,000 IU/kg (based on total body weight) and administered by vein infusion at a frequency of every 8-12 hours and continued for up to a maximum of six doses or as tolerated.
Other Names:
  • Aldesleukin
  • Interleukin
  • Proleukin

Drug: Mesna
Mesna given by vein continuously on Days -7 and -6.
Other Name: Mesnex

Behavioral: Questionnaires
Questionnaires completed one time between Day -21 and Day -14, at 12 weeks, and during follow up at Months 6, 12, 24.
Other Name: Survey

Experimental: Other Bone and Soft Tissue Sarcomas Drug: Cyclophosphamide
60 mg/kg/day by vein over approximately 2 hours on Days -7 and -6.
Other Names:
  • Cytoxan
  • Neosar

Drug: Fludarabine
25 mg/m2 by vein daily over approximately 15-30 minutes on Days -5 to -1.
Other Names:
  • Fludarabine Phosphate
  • Fludara

Biological: LN-145
LN-145 given by vein on Day 0.

Drug: IL-2
IL-2 infusion begin 3-24 hours after completion of the LN-145 infusion. IL-2 administered at a dose of 600,000 IU/kg (based on total body weight) and administered by vein infusion at a frequency of every 8-12 hours and continued for up to a maximum of six doses or as tolerated.
Other Names:
  • Aldesleukin
  • Interleukin
  • Proleukin

Drug: Mesna
Mesna given by vein continuously on Days -7 and -6.
Other Name: Mesnex

Behavioral: Questionnaires
Questionnaires completed one time between Day -21 and Day -14, at 12 weeks, and during follow up at Months 6, 12, 24.
Other Name: Survey




Primary Outcome Measures :
  1. Overall Response Rate (ORR) Evaluated by RECIST v1.1. [ Time Frame: Baseline up to 2 years after study treatment ]
    ORR 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%.


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) Evaluated by RECIST v1.1. [ Time Frame: Baseline up to 2 years after study treatment ]
    DCR derived as the sum of the number of patients who achieved PR/CR or SD per the RECIST v1.1 divided by the number of patients in the All-Treated analysis set x 100%.

  2. Duration of Response (DOR) Evaluated by RECIST v1.1. [ Time Frame: Baseline up to 2 years after study treatment ]
    DOR measured from the first time the per-visit response criteria are met for a confirmed complete response (CR) or partial response (PR) until the first date that progressive disease (PD) or death occurs.

  3. Progression-Free Survival (PFS) Evaluated by RECIST v1.1. [ Time Frame: Baseline up to 2 years after study treatment ]
    PFS defined as the time (in months) from the start date of lymphodepletion to progressive disease (PD) or death due to any cause, whichever event is earlier.

  4. Overall Survival (OS) [ Time Frame: Baseline up to 3 years after study treatment ]
    OS defined as the time (in months) from the start date of the lymphodepletion to death due to any cause.

  5. Adverse Events (AE) [ Time Frame: From first dose of Cyclophosphamide up to 30 days from the last dose of IL-2. ]
    Grade 3 or higher treatment-emergent AEs and their incidence rates compared descriptively to historical data of TIL in other cancer disease types. AE incidence rates estimated with 95% CIs per cohort and all cohorts combined.



Information from the National Library of Medicine

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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:

  1. Age between 18 and 70 (Subjects aged 16-70 may be enrolled into the osteosarcoma cohort).
  2. 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.
  3. Clinical performance status of ECOG 0 or 1 at enrollment and within 7 days of initiating lymphodepleting chemotherapy.
  4. 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.
  5. 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.
  6. Within 7 days of enrollment and with 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/mm^3; ALT/SGPT (alanine aminotransferase) and AST/SGOT (aspartate aminotransferase) </= 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; 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); Negative serum pregnancy test (female subjects of childbearing potential).
  7. Subjects must not have a confirmed human immunodeficiency virus (HIV) infection.
  8. Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms.
  9. 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.
  10. 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.
  11. Able to adhere to the study visit schedule and other protocol requirements.
  12. Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1 greater than 65% predicted or forced vital capacity (FVC) greater than 65% of predicted.
  13. Ovarian cancer cohort only: Subjects must have high-grade non-mucinous histology (carcinosarcomas are allowed).
  14. Ovarian cancer cohort only: Subjects must have platinum refractory or resistant disease.
  15. 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.
  16. 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.
  17. Other bone and soft tissue sarcomas cohort only: Subjects with other soft tissue sarcomas who have received at least one line of therapy.

Exclusion Criteria:

  1. Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system. PI or his/her designee shall make the final determination regarding appropriateness of enrollment.
  2. Patients with active viral hepatitis
  3. Patients who have a left ventricular ejection fraction (LVEF) < 45% at Screening.
  4. Patients with a history of prior adoptive cell therapies.
  5. Persistent prior therapy-related toxicities greater than Grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) v4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment.
  6. Primary immunodeficiency.
  7. History of organ or hematopoietic stem cell transplant.
  8. Chronic steroid therapy, however prednisone or its equivalent is allowed at </= 10 mg/day.
  9. Patients who are pregnant or nursing.
  10. Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his/her designee, would prevent adequate informed consent.
  11. 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 Sjorgen's syndrome will not be excluded.
  12. History of clinically significant chronic obstructive pulmonary disease (COPD), asthma, or other chronic lung disease.
  13. 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.
  14. 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.
  15. Has received a live vaccine within 30 days prior to the initiation of lymphodepletion.
  16. 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): NCT03449108


Contacts
Contact: Ljiljana Milojevic 713-792-8578 CR_Study_Registration@mdanderson.org
Contact: Virginia A Bayer, RN 713-563-3877 VRBayer@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Iovance Biotherapeutics, Inc.
Investigators
Principal Investigator: Amir A. Jazaeri, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03449108     History of Changes
Other Study ID Numbers: 2017-0672
NCI-2018-00918 ( Registry Identifier: NCI CTRP )
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: June 19, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant neoplasms of bone and articular cartilage
Malignant neoplasms of female genital organs
Cyclophosphamide
Cytoxan
Neosar
Fludarabine
Fludarabine phosphate
Fludara
LN-145
IL-2
Aldesleukin
Interleukin
Proleukin
Mesna
Questionnaires
Surveys

Additional relevant MeSH terms:
Neoplasms
Genital Neoplasms, Female
Bone Neoplasms
Cartilage Diseases
Soft Tissue Neoplasms
Neoplasms, Fibrous Tissue
Urogenital Neoplasms
Neoplasms by Site
Bone Diseases
Musculoskeletal Diseases
Connective Tissue Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Vidarabine
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic