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

NCT02420795 | Terminated Phase 1 Results FDA Drug

• 6 other identifiers: 2014-0630NCI-2015-00706204666201521421-909048-11159132
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D) (Phase I)

  21 days

• 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.

  Up to 63 days (first 3 courses)

Secondary Outcomes (2)

• Overall Survival (OS)

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

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

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

Study Arms (1)

Treatment (Akt/ERK inhibitor ONC201)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Akt/ERK Inhibitor ONC201 DRUG

Given PO

Also known as: ONC201, TIC10

Treatment (Akt/ERK inhibitor ONC201)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (Akt/ERK inhibitor ONC201)

Pharmacological Study OTHER

Correlative studies

Treatment (Akt/ERK inhibitor ONC201)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[MD Anderson Symptom Inventory (MDASI) completion only\]

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Lymphoma, Non-Hodgkin

Interventions

TIC10 compound

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Michael Wang, MD, Professor, Lymphoma-Myeloma
• Organization: UT MD Anderson Cancer Center

miwang@mdanderson.org

(713) 792-2860

Study Officials

• Luhua (Michael) Wang

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: November 3, 2015
• Primary Completion: November 16, 2020
• Study Completion: November 16, 2020
• Last Updated: April 4, 2022
• Results First Posted: April 4, 2022

Record last verified: 2022-03

Locations

US (1)