Safety and Efficacy of OT-82 in Participants With Relapsed or Refractory Lymphoma

NCT03921879 | Unknown Phase 1 FDA Drug

• 1 other identifier: OT-82-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma, Follicular; Lymphoma, Peripheral T-Cell; Lymphoma, Hodgkin

Outcome Measures

Primary Outcomes (5)

• Occurence 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.

  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.

  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.

  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.

  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.

  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.

Secondary Outcomes (5)

• Evaluate the Maximum Plasma Concentration (Cmax) of OT-82 in Human Participants

  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

  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

  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

  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

  Stage 1: Days 1,2,3,4,5,8,15,22, and 29; Stage 2: Days 1,2,8, and 15

Other Outcomes (2)

• Evaluate Tumor Tissue for Cancer Specific Genetic Mutations

  Days 1-21 of Cycle 1 treatment

• Evaluate Normal DNA Tissue

  Baseline (-14 days to -1 day before treatment)

Study Arms (2)

Stage 1 Dose Escalation

EXPERIMENTAL

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

Stage 2 Dose Expansion

EXPERIMENTAL

The dose expansion arm will use the maximum tolerated dose to determine preliminary efficacy.

Drug: OT-82 Dose Expansion

Interventions

OT-82 Dose Escalation DRUG

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.

Stage 1 Dose Escalation

OT-82 Dose Expansion DRUG

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.

Stage 2 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Provides signed informed consent before initiation of any study-specific procedures or treatment.
• Histologically (tumor tissue) confirmed diagnosis of lymphoma that has progressed despite prior treatment, and for which additional options leading to meaningful clinical benefit are not available. Lymphoma diagnoses may include the following:
• a. Confirmed histological diagnosis of the following types of B-cell Non-Hodgkin lymphoma (NHL): i. Low-grade B-cell NHLs including, but not limited to, FL, MCL, MZL, PMBL, LPC, or CLL/SLL. ii. Intermediate to high grade B-cell NHLs including, but not limited to DLBCL and other intermediate grade B-cell NHL, with disease progression following stem cell transplant or patient must be unwilling, unable or not an appropriate candidate for such. iii. Transformed Follicular Lymphoma. b. PTCL and others T-cell lymphoma, in which there is measurable non-cutaneous disease.
• c. Hodgkin's Lymphoma
• Measurable disease in all lymphoma classes except PTCL.
• Defined as nodal lesions \>1.5 cm or extra-nodal, non-cutaneous lesions \> 1.0 cm.
• Target lesions that have been previously irradiated and have not progressed since radiation are not considered measurable.
• Patients with PTCL may be eligible if they do not have measurable disease if they have skin disease.
• ECOG performance status of 0 or 1. This is a measure of a participant's ability to manage self care, mobility, work status, and other measures.
• Adequate baseline organ function.
• Adequate baseline hematologic (blood) function.
• Negative blood pregnancy test result obtained during screening if the patient is sexually mature woman who has not undergone a hysterectomy or ovary removal or has not been naturally postmenopausal for at least 24 consecutive months.
• Participant agrees to use acceptable contraceptive methods for the duration of time on the study, and continue to use acceptable contraceptive methods for 3 months after the last treatment with OT-82:
• Participant agrees to, and be capable of, adhering to the study visit schedule and other protocol requirements, including follow-up for survival.

You may not qualify if:

• Persistent clinically significant toxicities from previous anticancer therapy (excluding alopecia, which is permitted, and excluding Grades 2 and 3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the Investigator, and can be managed with available medical therapies).
• Treatment with cytotoxic, biologic, or targeted therapies for lymphoma within 14 days before administration of the patient's first dose of OT-82.
• Treatment with an investigational drug within 28 days before administration of the patient's first dose of OT-82.
• Treatment with a stem cell transplant with an infusion of stem cells no less than 8 weeks before administration of the patient's first dose of OT-82. There should be no graft versus host disease \> Grade 1 and participant should have discontinued all immunosuppressive therapy for such ≥ 2 weeks from OT-82 treatment.
• Radiation therapy within 14 days before administration of the patient's first dose of OT-82.
• Major surgical procedure within 28 days before administration of the patient's first dose of OT-82.
• Physical abnormality or medical condition that limits swallowing oral solutions, and/or has a history of non-adherence to oral therapies.
• Clinically significant gastrointestinal disorder that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Additional active malignancy that may confound the assessment of the study endpoints. If the participant has a past cancer history (i.e. active malignancy within 2 years before study entry) with substantial potential for recurrence, this must be discussed with the Sponsor before study enrollment. Patients with the following concomitant neoplastic diagnoses are eligible: nonmelanoma skin cancer and carcinoma in situ (including transitional cell carcinoma, cervical cancer, anal carcinoma, and melanoma in situ).
• Breastfeeding.
• Clinically significant cardiovascular disease including, but not limited to:
• Uncontrolled or any New York Heart Association Class III or IV congestive heart failure.
• Uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months before study entry.
• Systolic blood pressure \> 170 mm Hg or diastolic blood pressure \> 110 mm Hg, or clinically significant arrhythmias not controlled by medication.
• Average QTc interval by QTcF on triplicate ECGs at screening or baseline \> 470 msec (females) or \> 450 msec (male).

Sponsors & Collaborators

• Oncotartis, Inc.: lead

Study Sites (8)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma, Follicular; Lymphoma, T-Cell, Peripheral; Hodgkin Disease

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Eric Rowinsky, MD

  Oncotartis, Inc.

  STUDY DIRECTOR

Central Study Contacts

Olga Chernova, PhD

CONTACT

(716) 270-3232; ochernova@tartiscorp.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: April 19, 2019
• Study Start: July 29, 2019
• Primary Completion: April 1, 2021
• Study Completion: June 1, 2021
• Last Updated: October 23, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)