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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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 - 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]

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 - 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 - 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.


Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

M.D. Anderson Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Luhua (Michael) Wang
Principal Investigator Affiliation M.D. Anderson Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Central Nervous System Lymphoma, Gastric Mantle Cell Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Non-Hodgkin Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Non-Hodgkin Lymphoma, Splenic Mantle Cell Lymphoma
Study Website: View Trial Website
Additional Details


  • 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.
  • 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.

Arms & Interventions


Experimental: Treatment (Akt/ERK inhibitor ONC201)

Patients 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.


Drug: - Akt/ERK Inhibitor ONC201

Given PO

Other: - Laboratory Biomarker Analysis

Correlative studies

Other: - Pharmacological Study

Correlative studies

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

M D Anderson Cancer Center, Houston, Texas




M D Anderson Cancer Center

Houston, Texas, 77030

Site Contact

Luhua (Michael) Wang



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