This research study will test OT-82, which is an investigational ("research" or "experimental" ) drug. The study has two stages (Stage 1 and Stage 2). The purpose of Stage 1 is to determine the safety and tolerability and the maximum tolerated dose (MTD) or the maximum tested dose of OT-82 administered orally to participants. The purpose of Stage 2 is to determine the preliminary efficacy of OT-82 in relapsed or refractory lymphoma at the MTD or the maximum tested dose. Both parts of the study will also evaluate the pharmacokinetics (absorption, distribution, metabolism, elimination) of OT-82. OT-82 treatment slowed the growth, reduced the size, or in some cases cured certain cancers in animal studies. It is hoped that participants with relapsed or refractory lymphoma treated with OT - 82 in this study will experience slowing tumor growth and/or reduction of tumor size.
OT-82 affects an enzyme in the cancer cell called nicotinamide phosphoribosyltransferase (abbreviated NAMPT), which is involved with making energy for the cancer cell. OT-82 deprives the cancer cell of the energy that it needs to grow and divide. This is a Phase 1, non-randomized (all participants will receive the study medication), open-label (identity of the study drug will be known to the participant and the study staff), controlled (the methods of the study are not random) study. Approximately 45 -50 participants at approximately 10 study centers across the USA will take part in this research study. The starting dose for Stage 1 is 16.5 mg/m2 per day. Participants in Stage 1 will be assigned a dose dependent on when he or she entered the study. Doses will increase for each new group of 3 to 6 participants until the maximum tolerated dose (MTD) or the maximum tested dose is reached. OT-82 is an oral liquid suspension that will be taken by mouth once per day for 3 days followed by a 4-day rest period.. A participant may continue to receive treatment with OT-82 as long as the study doctor feels it is in their best interest; as long as the participant does not develop intolerable side effects; as long as the participant wishes to remain in the study; or as long as the sponsor does not close the study. Participants in Stage 2 of the study will receive either the MTD or the maximum tested dose of OT-82 determined in Stage 1. Assessment of anti-tumor activity will primarily focus on categorical objective response (Partial Response (PR) or Complete Response (CR)) as defined according to the consensus recommendations of the Lugano Classification criteria for malignant lymphoma (Cheson et al., 2014).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
The starting OT-82 dose level will be16.5mg/m2 given orally as an oral suspension once daily on Days 1-3, 8-10, and 15-17 of each successive 28-day cycle. Dose escalation will follow a modified 3+3 design. There is no maximum duration of OT-82 treatment; however, treatment will be discontinued if there is unacceptable toxicity, disease progression, withdrawal of consent by the patient, noncompliance with study requirements, intercurrent illness, development of symptoms or conditions listed as exclusion criteria, or closure of the study by the Sponsor.
A total of 25 patients evaluable for disease response will be treated with OT-82 on Days 1-3, 8-10, and 15-17 of the 28-day cycle at the MTD or maximum tested dose determined from Stage 1. This may include patients treated at that dose in Stage 1 plus expansion at that dose during Stage 2. Evaluability for disease response requires that patients receive at least one dose of OT-82. There is no maximum duration of OT-82 treatment; however, treatment will be discontinued if there is unacceptable toxicity, disease progression, withdrawal of consent by the patient, noncompliance with study requirements, intercurrent illness, development of symptoms or conditions listed as exclusion criteria, or closure of the study by the Sponsor.
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGCity of Hope National Medical Center
Duarte, California, United States
RECRUITINGSylvester Comprehensive Cancer Center
Miami, Florida, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITINGRoswell Park Cancer Institute
Buffalo, New York, United States
RECRUITINGUniversity Hospitals Seidman Cancer Center
Cleveland, Ohio, United States
RECRUITINGStephenson Cancer Center
Oklahoma City, Oklahoma, United States
RECRUITINGThomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
RECRUITINGOccurence of Dose Limiting Toxicities (DLT) in all participants during the Stage 1 Dose Escalation period
A DLT is a defined Adverse Events (AE) that limits the dosing schedule occurring during Cycle 1 regardless of Investigator attribution to OT-82.
Time frame: C1 (Days 1-28) through study completion.
Overall Response Rate in Participants with R/R Lymphoma
Evaluation of antitumor response in patients with lymphoma will be by the Lugano Classification criteria for malignant lymphoma. Participant with undergo Computed Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans for participants unable to have CT imaging. Overall response is derived from time-point response assessments as follows: * CR: Complete disappearance of all detectible clinical evidence of disease and disease-related symptoms if present before therapy. * PR: Regression of measurable disease and no new sites. * SD: Failure to attain CR, PR, or PD. * PD: Any new lesion or increase by ≥50% of previously involved sites at nadir.
Time frame: During Screening, at the end of Cycle 2 (C2) [each cycle is 28 days], then every 2 cycles thereafter until development of Progressive Disease (PD) up to week 24.
Response to OT-82 in Participants with Skin Involvement
Assessments will be made using the modified Severity Weighted Assessment Tool (mSWAT) and will include skin biopsies and/or photographs as indicated.
Time frame: Baseline (-14 days to -1 day before treatment), at the end of C1 and C2 (each cycle is 28 days), and every 2 cycles thereafter up to week 24.
Response to OT-82 in Participants with Bone Marrow Involvement
Bone marrow studies will be performed to confirm CR in patients with known bone marrow involvement. Bone marrow aspirates (±biopsy) will be assessed.
Time frame: Baseline (-14 days to -1 day before treatment) and at week 24.
Response to OT-82 in Participants with PTCL and known circulating clonal T lymphocytes
Relevant clonal T cell populations will be measured from peripheral blood samples during treatment with OT-82 and compared to baseline measures.
Time frame: Baseline (-14 days to -1 day before treatment), at the end of C1 and C2 (each cycle is 28 days), and every 2 cycles thereafter up to week 24.
Evaluate the Maximum Plasma Concentration (Cmax) of OT-82 in Human Participants
Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Cmax of OT-82 in human participants
Time frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15
Evaluate Time to Maximum Concentration (Tmax) of OT-82 in Human Participants
Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Cmax of OT-82 in human participants
Time frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15
Evaluate the Area Under the Curve (AUC) of OT-82 in Human Participants
Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the AUC of OT-82 in human participants
Time frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15
Evaluate the Clearance (Cl) of OT-82 in Human Participants
Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Clearance of OT-82 in human participants
Time frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15
Evaluate Visfatin Levels in Participants treated with OT-82
Visfatin, an enzyme involved in the mechanism of OT-82, will be measured with blood samples.
Time frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15
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