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TERMINATEDPHASE1/PHASE2

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

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

NCT02420795•M.D. Anderson Cancer Center

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 respond to treatment. Akt/ERK inhibitor ONC201 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: I. 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: I. 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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
•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
+3 more criteria

Exclusion Criteria

•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
•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
•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
+2 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

November 3, 2015

Primary Completion Date

November 16, 2020

Completion Date

November 16, 2020

Last Updated

April 4, 2022

Enrollment

ACTUAL participants

Conditions

Central Nervous System LymphomaGastric Mantle Cell LymphomaRecurrent Mantle Cell LymphomaRecurrent Non-Hodgkin LymphomaRefractory Mantle Cell LymphomaRefractory Non-Hodgkin LymphomaSplenic Mantle Cell Lymphoma

Interventions

Akt/ERK Inhibitor ONC201

DRUG

Laboratory Biomarker Analysis

OTHER

Pharmacological Study

OTHER

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NCT02203526

Primary Central Nervous System Lymphoma

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RECRUITINGPHASE2

Thiotepa in Combination With Pirtobrutinib (a BTK Inhibitor) and Sintilimab (a PD-1 Inhibitor) for Frail or Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma

NCT07416890

PirtobrutinibSintilimab+1 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 4, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma

Thiotepa in Combination With Pirtobrutinib (a BTK Inhibitor) and Sintilimab (a PD-1 Inhibitor) for Frail or Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma

Ultra Low Dose Radiation Delivered Before or After Chemotherapy-Free Targeted Therapy in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma

Zanubrutinib in Combination With Sonrotoclax for the Treatment of Underrepresented Ethnic and Racial Minorities With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL)