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Central Nervous System LymphomaPhase 1/2NCT02420795

Akt/ERK Inhibitor ONC201 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

A Phase 1/2 study testing Akt/ERK Inhibitor ONC201, Laboratory Biomarker Analysis and Pharmacological Study in people with Central Nervous System Lymphoma and Gastric Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects and the best dose of v-akt murine thymoma viral oncogene homolog (Akt)/mitogen-activated protein kinase 1(ERK) inhibitor ONC201 and to see how well it works in treating patients with non-Hodgkin's lymphoma that has returned after a period of improvement or does not… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Akt/ERK Inhibitor ONC201, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
3 Nov 2015to 16 Nov 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Phase 1 and Phase 2: confirmed diagnosis of previously treated relapsed and/or refractory lymphoma; patients with central nervous system (CNS) lymphoma are included
  • Patient with leukemia phase (peripheral blood involvement), CNS lymphoma [including cerebrospinal fluid (CSF)-only disease], non-measurable disease, gastrointestinal (GI) mantle cell lymphoma (MCL), or bone marrow (BM) MCL are also eligible; gastrointestinal or bone marrow or spleen only patients are allowable and will be analyzed separately
  • All adverse events related to prior therapies (chemotherapy, radiotherapy, and/or surgery) must be resolved to =< grade 1, except for alopecia
  • Patients must be willing to receive transfusions of blood products
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
  • Serum creatinine < 2.0 mg/dl
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  • Serum bilirubin < 1.5 mg/dl
  • Platelet count > 50,000/mm^3
  • Absolute neutrophil count (ANC) > 1,000/mm^3
  • Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present
  • Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test and must be willing to use acceptable methods of birth control during the study and for 90 days after the last dose of study treatment; acceptable methods of birth control include condoms with birth control foam, birth control pills, implantable or injectable birth control, birth control patch, intrauterine device (IUD), or diaphragm with spermicidal gel; male patients must use an effective barrier method of contraception (i.e. , condoms with birth control foam or diaphragm with spermicidal gel) during the study and for 90 days following the last dose of study treatment if sexually active with a female of childbearing potential; contraception must be in place at least 2 weeks prior to initiating study treatment; a female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must be English-speaking [MD Anderson Symptom Inventory (MDASI) completion only]

Who cannot join

  • Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled infection, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk or would prevent the subject from signing the informed consent form
  • Pregnant or breast feeding females
  • Use of any standard/experimental anti-lymphoma drug therapy, including steroids (dexamethasone dose >= 4 mg/day or prednisone >= 20 mg/day), within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment; hydroxyurea is permitted up to 24 hours before the first dose of study drug in patients with rapidly-proliferating disease
  • Prior allogeneic stem cell transplant (SCT) within 16 weeks or autologous SCT within 8 weeks of initiation of therapy (patients that require immunosuppressive therapy are not eligible within 60 days of therapy)
  • History of human immunodeficiency virus (HIV) infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody); hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation; HIV screening is not required for this study
  • Significant neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to enrollment
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  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of ONC201
  • Major surgery within 4 weeks of initiation of therapy
  • The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent; investigator discretion is allowed
  • Patients with New York Heart Association (NYHA) class III and IV heart failure, myocardial infarction in the preceding 6 months, and significant conduction abnormalities, including but not limited to second (2nd) degree atrioventricular (AV) block type II, third (3rd) degree block, QT prolongation (corrected QT [QTc] > 500 msec), sick sinus syndrome, ventricular tachycardia, symptomatic bradycardia (heart rate < 50 beats per minute [bpm]), hypotension, light headedness and syncope; patients with active atrial fibrillation will be excluded; the protocol excludes patients who have within the past year had a stent and by recommendation of their cardiologist need to stay on anticoagulants such as warfarin equivalent vitamin K antagonist
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC201 or its excipients
  • Acute infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of study
  • Active alcoholism or use of recreational drug (evaluated by history taking)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Study of Oral ONC201 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma

This phase I/II trial studies the side effects and the best dose of v-akt murine thymoma viral oncogene homolog (Akt)/mitogen-activated protein kinase 1(ERK) inhibitor ONC201 and to see how well it works in treating patients with non-Hodgkin's lymphoma that has returned after a period of improvement or does not respond to treatment. Akt/ERK inhibitor ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine recommended phase II dose for oral ONC201 (Akt/ERK inhibitor ONC201) in patients with relapsed/refractory lymphomas. (Phase I) II. To identify toxicities associated with oral ONC201 in patients with relapsed/refractory lymphomas. (Phase I) III. To determine the objective response rate to ONC201 in patients with relapsed/refractory lymphomas. (Phase II)

SECONDARY OBJECTIVES:

  1. To determine the pharmacokinetics (PK) of oral ONC201 following administration. (Phase I) II. To observe the anti-tumor effects of oral ONC201, if any occur, in patients with relapsed/refractory lymphomas. (Phase I) III. Confirm tolerability of recommended phase II dose. (Phase II) IV. Assess clinical outcomes associated with ONC201 treatment in patients with relapsed/refractory lymphomas. (Phase II) V. Correlate clinical outcome with tumor and serum biomarkers. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive Akt/ERK inhibitor ONC201 orally (PO) on day 1 of every cycle or day 1 of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Akt/ERK Inhibitor ONC201, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin

What participants receive

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

  • Akt/ERK Inhibitor ONC201Drug

    Also called ONC201, TIC10

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02420795
Study groupRoleWhat they receive
Treatment (Akt/ERK inhibitor ONC201)ExperimentalPatients receive Akt/ERK inhibitor ONC201 PO on day 1 of every cycle or day 1 of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Akt/ERK Inhibitor ONC201; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

  1. Recommended Phase 2 Dose (RP2D) (Phase I)

    Measured: 21 days

  2. Number of Participants With Overall Response Rate (Phase 1 and 2)

    Defined as either progressive disease or stable disease observed assessed by the Revised International Workshop Standardization Response Criteria for non-Hodgkin lymphoma.

    Measured: Up to 63 days (first 3 courses)

Secondary outcomes (2)

  1. Overall Survival (OS)

    Overall survival is the time in months from start of study treatment to date of death due to any cause.

    Measured: every 3 months for 1 year, then every 6 months, up to 3 years

  2. Progression-free Survival (PFS)- (Phase 2)

    Progression free survival is defined as time in weeks from start of study treatment to first documentation of objective tumor progression or up to death due to any cause, whichever occurs first.

    Measured: every 3 months for 1 year, then every 6 months, up to 6 years

Timeline

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

  1. First posted20 Apr 2015 (estimated)
  2. Study start3 Nov 2015
  3. Primary completion16 Nov 2020
  4. Study completion16 Nov 2020

Why it stopped: Per PI Request

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02420795
Sponsor's protocol ID
2014-0630
Other IDs
NCI-2015-00706, 204666, 20152142, 1-909048-1, 1159132, 2014-0630
Status last verified
Mar 2022
First submitted
15 Apr 2015
Last updated
4 Apr 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Akt/ERK Inhibitor ONC201, Laboratory Biomarker Analysis and Pharmacological Study in people with Central Nervous System Lymphoma and Gastric Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 13 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: stopped early, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Recommended Phase 2 Dose (RP2D) (Phase I) (time frame: 21 days). 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 NCT02420795.

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 4 Apr 2022.

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