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Advanced Hematological DisordersPhase 1NCT03048344

A Phase I, Two-part Study to Determine the Recommended Dose and Evaluate the Safety and Tolerability of a Novel Oral Arsenic Trioxide Formulation (ORH-2014) in Subjects With Advanced Hematological Disorders

A Phase 1 study testing ORH-2014 in people with Advanced Hematological Disorders, run by Orsenix LLC at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Part 1 will be conducted as an open-label, non-randomized, non-placebo-controlled dose escalation study using pre-specified doses. Subjects with the following advanced hematological disorders and no available therapies, and who satisfy all inclusion/exclusion criteria will be enrolled. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hematological Disorders
What is being tested?
ORH-2014
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
4 sitesUnited States
Study dates
2 Dec 2016to 28 Feb 2019
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

  • Female and male subjects ≥18 years of age with one of the following:
  • Relapsed or refractory acute myelocytic leukemia (AML) with nucleophosmin-1 (NPM1) mutations and no available therapies.
  • Relapsed or refractory acute promyelocytic leukemia (APL), with no available therapies. Note: Prior exposure to arsenic trioxide is allowed; however, subjects who have failed arsenic trioxide within the last 12 months are not allowed.
  • Relapsed or refractory myelodysplastic syndrome (MDS), International Prognostic Scoring System intermediate or high-risk, with no available therapies
  • Relapsed or refractory chronic myelomonocytic leukemia (CMML), and other MDS/myeloproliferative neoplasm (MPN) overlap syndromes, with no available therapies
  • Relapsed or refractory mantle cell lymphoma (MCL) with no adequate therapies.
  • Negative pregnancy test at the Screening visit for women of childbearing potential and willingness to use adequate birth control
  • Not willing to undergo, not a candidate for, or not having a donor for immediate (within 3 months from the Screening date) bone marrow transplantation.

Who cannot join

  • Eastern Cooperative Oncology Group performance status of ≥3;
  • Absolute myeloblast count ≥20,000/mm^3;
  • Administration of any antineoplastic therapy within 5 half-lives of the antineoplastic therapy before the first dose of ORH-2014, with the exception of hydroxyurea that should be discontinued 1 day prior to the first dose of ORH-2014
  • Presence of any remaining toxicities due to previous chemotherapy
  • Participation in other clinical trials within at least 2 weeks of the first ORH-2014 dose;
  • Clinical evidence of active central nervous system leukemia;
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  • Active and uncontrolled infection
  • Major surgery within 2 weeks prior to trial entry;
  • Liver function tests above the following limits at Screening: total bilirubin >1.5 x upper limit of normal (ULN) unless related to Gilbert's syndrome or hemolysis; aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x ULN; for subjects with liver involvement, AST and/or ALT >5 x ULN;
  • Serum creatinine >1.5 x ULN and/or creatinine clearance or estimated glomerular filtration rate <30 mL/min
  • Impaired cardiac function
  • Myocardial infarction of unstable angina within 6 months prior to the planned start date of study drug.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • MD Anderson

    Houston, Texas, 77030

  • Vanderbilt University

    Nashville, Tennessee, 37240

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medical College

    New York, New York, 10065

Other trials in United States

About this study

Part 1 will be conducted as an open-label, non-randomized, non-placebo-controlled dose escalation study using pre-specified doses. Subjects with the following advanced hematological disorders and no available therapies, and who satisfy all inclusion/exclusion criteria will be enrolled. The purpose is to identify the recommended dose of oral ORH-2014 in subjects with advanced hematological disorders.

Part 2 will be an expansion phase conducted as a single-arm, open-label study to further evaluate the safety and tolerability of ORH-2014 at the maximum tolerated dose (MTD) or recommended dose determined from Part 1 in the fasted state. Subjects with the same disease types as in Part 1 will be enrolled. All subjects will receive oral ORH-2014, in the fasted state, at the recommended dose for an initial period of up to 12 weeks. The purpose is to evaluate the safety and tolerability of oral ORH-2014 in a population of subjects with advanced hematological disorders when administered at the recommended dose.

Being tested
ORH-2014
Keywords
acute promyelocytic leukemia, APL, arsenic trioxide
Medical subject headings
Leukemia, Promyelocytic, Acute

What participants receive

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

  • ORH-2014Drug

    ORH-2014 capsule 5 mg orally with dose escalations of 5 mg intervals.

  • ORH-2014Drug

    ORH-2014 capsule at recommended dose orally.

Study groups in NCT03048344
Study groupRoleWhat they receive
Part 1ExperimentalSubjects will receive oral ORH-2014 at a planned starting dose of 5 mg once daily (QD) in the fasted state. If escalation criteria are met, the administered dose will increase by 5 mg increments to a maximum of 50 mg QD. The starting daily dose is approximately half the typical IV dose (0.15 milligram per kilogram [mg/kg]) extrapolated to a 70-kg person.
Receives: Drug: ORH-2014
Part 2ExperimentalSubjects will receive a daily oral dose of ORH-2014 at the recommended dose identified in Part 1. ORH-2014 will be administered in the fasted state.
Receives: Drug: ORH-2014

What is being measured

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

  1. To identify the recommended dose

    The recommended dose is determined by the number of patients who experience a dose limiting toxicity (DLT).

    Measured: From baseline to Week 4

  2. Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability of ORH-2014 when administered at the MTD or recommended dose

    To evaluate safety and tolerability the aggregate review will include but is not limited to:

    • NCI-CTCAE Grade 3 and 4 AEs, serious adverse events (SAEs), deaths;
    • Laboratory results;
    • Vital signs;
    • ECGs;
    • Individual subject profiles including, but not limited to: medical history, AEs, concomitant medications, laboratory results, and vital signs;
    • Subject disposition and screen failure rates.

    Measured: Up to Week 28

Secondary outcomes (13)

  1. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by maximum observed concentration (Cmax)

    Measured: Baseline up to Week 24

  2. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by time to maximum concentration (Tmax)

    Measured: Baseline up to Week 24

  3. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by apparent terminal elimination half-life (t1/2)

    Measured: Baseline up to Week 24

  4. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by area under the concentration-time curve from 0 to 24 hours (AUC0-24)

    Measured: Baseline up to Week 24

  5. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by area under the concentration-time curve extrapolated to infinity (AUC0-infinity)

    Measured: Baseline up to Week 24

  6. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by apparent terminal elimination rate constant (λZ)

    Measured: Baseline up to Week 24

  7. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by apparent total clearance (CL/F)

    Measured: Baseline up to Week 24

  8. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by apparent total clearance normalized by body weight (CL/F/kg)

    Measured: Baseline up to Week 24

  9. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by apparent total volume of distribution (Vz/F)

    Measured: Baseline up to Week 24

  10. To determine the plasma pharmacokinetic (PK) profiles of total arsenic as measured by accumulation ratio (AR)

    Measured: Baseline up to Week 24

  11. To evaluate the effect of ORH-2014 on QT-interval corrected for heart rate using Fridericia's formula (QTcF)

    Measured: Baseline up to Week 28

  12. Safety Assessment during the expansion phase of the study on the effect of oral ORH-2014 on safety parameters

    During the expansion phase of the study, an aggregate clinical data review (ACDR) will be conducted. This review will collect data from electronic data capture, the ECG central review vendor (ERT), and other sources to include but is not limited to:

    • NCI-CTCAE Grade 3 and 4 AEs, SAEs, deaths;
    • Laboratory results;
    • Vital signs;
    • ECG's;
    • Individual subject profiles including, but not limited to: medical history, AEs, concomitant medications, laboratory results, and vital signs;
    • Subject disposition and screen failure rates.

    Measured: Baseline up to Week 28

  13. The number of participants with a complete response (CR) or partial response (PR) according to International Working Group (IWG) response criteria

    Bone marrow aspirates and/or biopsies will be obtained at the designated timepoints for evaluation of efficacy. Response criteria will be according to the International Working Group. Responders are participants who obtain complete remission (CR) or partial remission (PR), with or without cytogenetic response, and marrow complete remission.

    Measured: Up to Week 24

Timeline

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

  1. First posted9 Feb 2017 (estimated)
  2. Study start2 Dec 2016
  3. Primary completion28 Feb 2019
  4. Study completion28 Feb 2019

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
Part 1 of the study is parallel. Part 2 will be an expansion phase.
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03048344
Sponsor's protocol ID
ORH2014-001
Status last verified
Mar 2019
First submitted
31 Jan 2017
Last updated
25 Mar 2019
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Ravandi F, Koumenis I, Johri A, Tallman M, Roboz GJ, Strickland S, Garcia-Manero G, Borthakur G, Naqvi K, Meyer M, Pudipeddi M, Nidarmarthy S, Vaddi K, Kantarjian H. Oral arsenic trioxide ORH-2014 pharmacokinetic and safety profile in patients with advanced hematologic disorders. Haematologica. 2020 Jun;105(6):1567-1574. doi: 10.3324/haematol.2019.229583. Epub 2019 Sep 26.

    PubMed 31558670

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ORH-2014 in people with Advanced Hematological Disorders, run by Orsenix LLC at 4 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 8 inclusion and 12 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: finished, as of the sponsor's last update on 25 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To identify the recommended dose (time frame: From baseline to Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03048344, which also lists 1 linked publication.

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 25 Mar 2019.

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