Safety and Efficacy of OT-82 in Participants With Relapsed or Refractory Lymphoma
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|ClinicalTrials.gov Identifier: NCT03921879|
Recruitment Status : Unknown
Verified October 2020 by Oncotartis, Inc..
Recruitment status was: Recruiting
First Posted : April 19, 2019
Last Update Posted : October 23, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, T-Cell Lymphoma, Follicular Lymphoma, Peripheral T-Cell Lymphoma, Hodgkin||Drug: OT-82 Dose Escalation Drug: OT-82 Dose Expansion||Phase 1|
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 (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Study OT-82-001 is a Phase 1, non-randomized, controlled, first-in-human, two stage (dose escalation and dose expansion) study evaluating multiple doses and schedules of orally administered OT-82 in patients with R/R lymphoma|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of OT-82 in Patients With Relapsed or Refractory Lymphoma|
|Actual Study Start Date :||July 29, 2019|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||June 2021|
Experimental: Stage 1 Dose Escalation
The dose escalation arm will use a modified 3+3 design to determine the maximum tolerated dose. or maximum tested dose.
Drug: OT-82 Dose Escalation
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.
Experimental: Stage 2 Dose Expansion
The dose expansion arm will use the maximum tolerated dose to determine preliminary efficacy.
Drug: OT-82 Dose Expansion
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.
- Occurence of Dose Limiting Toxicities (DLT) in all participants during the Stage 1 Dose Escalation period [ Time Frame: C1 (Days 1-28) through study completion. ]A DLT is a defined Adverse Events (AE) that limits the dosing schedule occurring during Cycle 1 regardless of Investigator attribution to OT-82.
- Overall Response Rate in Participants with R/R Lymphoma [ 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. ]
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.
- Response to OT-82 in Participants with Skin Involvement [ 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. ]Assessments will be made using the modified Severity Weighted Assessment Tool (mSWAT) and will include skin biopsies and/or photographs as indicated.
- Response to OT-82 in Participants with Bone Marrow Involvement [ Time Frame: Baseline (-14 days to -1 day before treatment) and at week 24. ]Bone marrow studies will be performed to confirm CR in patients with known bone marrow involvement. Bone marrow aspirates (±biopsy) will be assessed.
- Response to OT-82 in Participants with PTCL and known circulating clonal T lymphocytes [ 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. ]Relevant clonal T cell populations will be measured from peripheral blood samples during treatment with OT-82 and compared to baseline measures.
- Evaluate the Maximum Plasma Concentration (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 ]Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Cmax of OT-82 in human participants
- Evaluate Time to Maximum Concentration (Tmax) 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 ]Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Cmax of OT-82 in human participants
- Evaluate the Area Under the Curve (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 ]Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the AUC of OT-82 in human participants
- Evaluate the Clearance (Cl) 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 ]Blood samples taken prior to administration of the OT-82 dose will be assessed to determine the Clearance of OT-82 in human participants
- Evaluate Visfatin Levels in Participants treated with OT-82 [ Time Frame: Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15 ]Visfatin, an enzyme involved in the mechanism of OT-82, will be measured with blood samples.
- Evaluate Tumor Tissue for Cancer Specific Genetic Mutations [ Time Frame: Days 1-21 of Cycle 1 treatment ]Tumor tissue will be collected from the most recent archived tumor biopsy sample.
- Evaluate Normal DNA Tissue [ Time Frame: Baseline (-14 days to -1 day before treatment) ]Obtain DNA samples from the cheek of participants (buccal) to determine if genetic alterations are tumor-specific.
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): NCT03921879
|Contact: Olga Chernova, PhD||(716) firstname.lastname@example.org|
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|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
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|Contact: Sami Ibrahimi, MD|
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|Thomas Jefferson University Hospital||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Neil Palmisiano, MD|
|Study Director:||Eric Rowinsky, MD||Oncotartis, Inc.|