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LymphomaPhase 1NCT03921879

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

A Phase 1 study testing OT-82 Dose Escalation and OT-82 Dose Expansion in people with Lymphoma and Lymphoma, Non-Hodgkin, run by Oncotartis, Inc. at 8 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell
What is being tested?
OT-82 Dose Escalation and OT-82 Dose Expansion
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
8 sitesUnited States
Study dates
29 Jul 2019to Jun 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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.
  • Hodgkin's Lymphoma
  • Measurable disease in all lymphoma classes except PTCL.
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  • 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.

Who cannot join

  • 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.
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  • 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).
  • History of additional risk factors for a cardiac condition known as torsade de pointes (e.g., heart failure, low potassium, family history of long QT syndrome, use of concomitant medications that prolong the cardiac QT/QTc interval).
  • Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the opinion of the Investigator, would put the patient at significant risk for pulmonary complications during the study (patient must not be dependent on oxygen).
  • History of brain or leptomeningeal malignant disease (CNS imaging is not required before study entry unless there is a clinical suspicion of CNS involvement).
  • Primary CNS lymphoma.
  • Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days before administration of the patient's first dose of OT-82. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Uncontrolled illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known positive status for HIV and:
  • Not receiving optimal anti-HIV therapy
  • Demonstrated to be noncompliant with anti-HIV therapy.
  • Has evidence of worsening HIV viral load (as assessed by HIV real-time qPCR).
  • Not willing to attend HIV clinic follow-up at appropriate intervals.
  • Active or chronic hepatitis B or hepatitis C (screening is not required).
  • Any medical condition that, in the opinion of the Investigator, places the patient at unacceptably high risk for toxicity.
  • Anticoagulation with warfarin or a direct thrombin inhibitor; a washout period of 7 days before administration of a patient's first dose of study drug is required for patients who are taken off these treatments (treatment with low molecular weight heparin is allowed).
  • Requires a medication(s) that is a strong inhibitor of cytochrome CYP3A4 (boceprevir,clarithromycin, cobicistat, conivaptan, diltiazem, anoprevir/ritonavir, elvitegravir/ritonavir, grapefruit juice, idelasib, indinavir/ritonavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, paritaprevir/ritonavir/ombitasvir and/or dasabuvir, posaconazole, ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, troleandomycin, voriconazole, and telithromycin).
  • Requires a medication(s) that is a strong inducer of CYP3A4 (carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, and St John's wort).
  • Requires a medication(s) that is a strong inhibitor of P-glycoprotein (P-gp) (amiodarone, carvedilol, clarithromycin, cyclosporine, dronedarone, elacridar, itraconazole, ketoconazole, lapatinib, lopinavir/ritonavir, propafenone, quinidine, ranolazine, reserpine, ritonavir, saquinavir/ritonavir, tacrolimus, telaprevir, tipranavir/ritonavir, verapamil).

Trial locations and contacts

8 sites in 1 country.

Olga Chernova, PhD contact

(716) 270-3232

ochernova@tartiscorp.com

8 sites in 1 country

United States8 sites, 8 recruiting
  • University of Michigan

    Ann Arbor, Michigan, 48109

    Tycel J Phillips, MD

    Recruiting
  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Amitkumar Mehta, MD

    Recruiting
  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

    Francisco J Hernandez-Ilizaliturri, MD

    Recruiting
  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

    Paolo Caimi, MD

    Recruiting
  • City of Hope National Medical Center

    Duarte, California, 91010

    Jasmine M Zain, MD

    Recruiting
  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

    Alvaro J Alencar, MD

    Recruiting
  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

    Sami Ibrahimi, MD

    Recruiting
  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

    Neil Palmisiano, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Study of OT-82 in Patients With Relapsed or Refractory Lymphoma

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.

Read the detailed description

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).

Being tested
OT-82 Dose Escalation, OT-82 Dose Expansion
Medical subject headings
Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Lymphoma, T-Cell, Lymphoma, Follicular, Lymphoma, T-Cell, Peripheral, Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OT-82 Dose EscalationDrug

    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.

  • OT-82 Dose ExpansionDrug

    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.

Study groups in NCT03921879
Study groupRoleWhat they receive
Stage 1 Dose EscalationExperimentalThe dose escalation arm will use a modified 3+3 design to determine the maximum tolerated dose. or maximum tested dose.
Receives: Drug: OT-82 Dose Escalation
Stage 2 Dose ExpansionExperimentalThe dose expansion arm will use the maximum tolerated dose to determine preliminary efficacy.
Receives: Drug: OT-82 Dose Expansion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: C1 (Days 1-28) through study completion.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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.

  4. 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.

    Measured: Baseline (-14 days to -1 day before treatment) and at week 24.

  5. 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.

    Measured: 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)
  1. 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

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

  2. 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

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

  3. 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

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

  4. 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

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

  5. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2019
  2. Study start29 Jul 2019
  3. Primary completionApr 2021 (estimated)
  4. Study completionJun 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
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)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03921879
Sponsor's protocol ID
OT-82-001
Status last verified
Oct 2020
First submitted
12 Mar 2019
Last updated
23 Oct 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing OT-82 Dose Escalation and OT-82 Dose Expansion in people with Lymphoma and Lymphoma, Non-Hodgkin, run by Oncotartis, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Olga Chernova, PhD ((716) 270-3232, ochernova@tartiscorp.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2020.

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