LN-145 in Treating Patients With Relapsed or Refractory Ovarian Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas
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|ClinicalTrials.gov Identifier: NCT03449108|
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : May 10, 2019
|Condition or disease||Intervention/treatment||Phase|
|Bone Sarcoma Dedifferentiated Chondrosarcoma Giant Cell Tumor of Bone Malignancy in Giant Cell Tumor of Bone Ovarian Carcinosarcoma Platinum-Resistant Ovarian Carcinoma Recurrent Osteosarcoma Refractory Osteosarcoma Refractory Ovarian Carcinoma Soft Tissue Sarcoma Undifferentiated High Grade Pleomorphic Sarcoma of Bone||Biological: Aldesleukin Biological: Autologous Tumor Infiltrating Lymphocytes LN-145 Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 2|
I. To evaluate efficacy using objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in each cohort.
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.
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).
Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, fludarabine phosphate IV over 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.
After completion of study treatment, participants are followed up at 18 weeks, 6, 9, 12, 18 and 24 months, then every 3 months for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 31, 2020|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (combination chemotherapy, LN-145, aldesleukin)
Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, fludarabine phosphate IV over 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.
Biological: Autologous Tumor Infiltrating Lymphocytes LN-145
Drug: Fludarabine Phosphate
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Objective response rate [ Time Frame: Up to 3 years ]Assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Estimation will use 80% confidence intervals by the Wilson score method.
- Disease control rate [ Time Frame: Up to 3 years ]
- Duration of response [ Time Frame: Up to 3 years ]
- Progression free survival [ Time Frame: Up to 3 years ]Will be summarized using Kaplan-Meier estimates.
- Overall survival [ Time Frame: Up to 3 years ]Will be summarized using Kaplan-Meier estimates.
- Incidence of adverse events of adoptive cell therapy with tumor infiltrating lymphocytes (TIL) across multiple tumor types [ Time Frame: Up to 3 years ]
- Duration of TIL persistence [ Time Frame: Up to 3 years ]Determined by T-cell receptor (TCR) sequencing of infused T cells serially isolated following LN-145 infusion, or alternatively iRepertoire assessment of messenger ribonucleic acid for the TCRs.
- Response as determined by the immune-related response criteria [ Time Frame: Up to 3 years ]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.
- Immunological phenotype of LN-145 by multichannel flow cytometry [ Time Frame: Day 0 ]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.
- Tumor assessment via immunohistochemistry, TCR sequencing, and transcriptional analysis [ Time Frame: Baseline up to 3 years ]Paired t-test will be used to examine the molecular and immunological features of tumors before and after TIL therapy.
- Health Related Quality of Life [ Time Frame: Up to 24 months ]Assessed per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) questionnaire.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449108
|Contact: Ljiljana Milojevic||713-792-8578||CR_Study_Registration@mdanderson.org|
|Contact: Virginia A Bayer, RN||713-563-3877||VRBayer@mdanderson.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Amir A. Jazaeri 713-745-1613|
|Principal Investigator: Amir A. Jazaeri|
|Principal Investigator:||Amir A Jazaeri||M.D. Anderson Cancer Center|