A Global Study of the PETAL Consortium

Study Overview
=================
Brief Summary
-----------------
The goal of this observational study is to correlate molecular alterations with outcomes including overall survival (OS), progression-free survival (PFS) for patients with a new diagnosis, primary refractory or relapse, of mature T-cell and NK-cell neoplasms (TNKL). We hypothesize that machine learning will uncover distinct genetic vulnerabilties that underlie treatment response and resistance for patient with TNKL.

Detailed Description
-----------------
This study is a prospective longitudinal observational study of newly diagnosed and relapsed/refractory patients with T-cell and NK -cell neoplasm at participating institutions. Patients will be enrolled in the study during the course of their first visit as a new patient at the participating institution and followed for up to 4 years through the course of their clinical management. Routine demographics, baseline clinical features, including pathology, molecular information related to the tumor, radiology, treatment characteristics and quality of life (QoL) related to their lymphoma care will be collected over the course of 4 years by clinical research teams at every participating institution. This data will be de-identified data and then shared through a secure and password protected REDCap with other participating institutions under data usage agreements of the consortium agreement. Next generation sequencing including but not limited to such as whole exome sequencing and bulk RNA-sequencing will be performed on archived lymphoma specimens and on mononuclear cells, cfDNA and saliva (when feasible) for detailed molecular characterization of the tumor. Molecular correlation with outcomes will be performed. Deep learning algorithms will be utilized to predict response and survival of lymphoma subtypes and in heterogeneous clinical scenarios and to various potential therapeutic approaches that the patient has not been exposed to.

Official Title
-----------------
Integration of Machine Learning and Genomics to Predict Outcomes for Newly Diagnosed, Relapsed and Refractory Mature T-cell and NK/T-cell Lymphomas: a Global Study of the PETAL Consortium

Conditions
-----------------
T-Cell and NK-Cell Neoplasm

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Untreated, relapsed, or refractory histologically confirmed mature T-cell or NK-cell neoplasm. All subtypes of PTCL are eligible except for T-cell large granular lymphocytic leukemia, cutaneous T-cell lymphoma such as but not limited to mycosis fungoides and transformation, Sézary syndrome, and primary cutaneous CD30+ disorders. Exclusion Criteria: Precursor T/NK neoplasms, T-cell large granular lymphocytic leukemia, cutaneous T-cell lymphoma such as but not limited to mycosis fungoides and transformation, Sézary syndrome, and primary cutaneous CD30+ disorders. Adults who are unable to consent, individuals who are not yet adults such as infants, children and teenagers, pregnant women, and prisoners.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Massachusetts General Hospital, Boston, USA<br>Participating investigators at various institutions will perform weekly review of their new patients with PTCL (newly diagnosed or relapsed/refractory) on the outpatient and inpatient clinical services with their clinical research teams to identify potential subjects for enrollment based on the above inclusion/exclusion criteria. Expected enrollment is anticipated to be up to 30 patients per site per year. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Difference in overall survival (OS) in subjects with primary refractory versus relapsed mature T-cell and NK-cell neoplasms at the completion of 4 years. | Up to 4 Years | 
| Progression-free Survival | Difference in progression-free survival (PFS) in subjects with primary refractory versus relapsed mature T-cell and NK-cell neoplasms at the completion of 4 years. | Up to 4 Years | 
| Duration of Response | Difference in duration of response in subjects with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice at the completion of 4 years. | Up to 4 Years | 
| Time to progression | Difference in time to progression in subjects with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice at the completion of 4 years. | Up to 4 Years | 
| Number of subjects proceeding to stem cell transplantation | Difference in number of subjects bridged to stem cell transplantation (allogeneic or autologous) with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice at the completion of 4 years. | Up to 4 Years | 
| Association of tumor specific somatic variants with treatment response | Determine whether tumor specific somatic variants identified at the time of diagnosis predicts response to treatment in subjects with mature T-cell and NK-cell neoplasms at the completion of 4 years in at least 50% of the patients. | Up to 4 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | Difference in complete response rate in subjects with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice. | Up to 4 Years | 
| Overall Response Rate | Difference in overall response rate in subjects with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice. | Up to 4 Years | 
| Rate of Adverse Events | Frequency of adverse events in subjects with mature T-cell and NK-cell neoplasms treated with cytotoxic chemotherapy versus prespecified non-chemotherapeutic choice using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Up to 4 Years |