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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02420795
Recruitment Status : Terminated (Per PI Request)
First Posted : April 20, 2015
Last Update Posted : November 23, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE April 15, 2015
First Posted Date  ICMJE April 20, 2015
Last Update Posted Date November 23, 2020
Actual Study Start Date  ICMJE November 3, 2015
Actual Primary Completion Date November 16, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • Recommended phase 2 dose (RP2D) (Phase I) [ Time Frame: 21 days ]
  • Dose limiting toxicity (DLT) rate (Phase I) [ Time Frame: Up to 21 days ]
    DLT rate will be summarized by frequency and 95% confidence interval. Toxicity will be summarized by dose levels, by grade and by their relationship to treatment.
  • Overall response rate (Phase II) [ Time Frame: Up to 63 days (first 3 courses) ]
    Defined as either complete response or partial response observed assessed by the Revised International Workshop Standardization Response Criteria for non-Hodgkin lymphoma. Overall response rate will be summarized by frequency and 95% confidence interval.
  • Incidence of adverse events of RP2D (Phase Ii) [ Time Frame: Up to 30 days post treatment ]
    A Bayesian method will be used for toxicity monitoring. Toxicity will be summarized by dose levels, by grade and by their relationship to the treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: April 17, 2015)
Maximum Tolerated Dose (MTD) of ONC201 to Determine the Recommended Phase 2 Dose [ Time Frame: 21 days ]
MTD defined as the highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • Overall survival (OS) [ Time Frame: Up to 6 years ]
    OS will be estimated by the method of Kaplan and Meier analysis. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.
  • Progression-free survival (PFS) [ Time Frame: Up to 6 years ]
    PFS will be estimated by the method of Kaplan and Meier analysis. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2015)
Overall Response (OR) [ Time Frame: 21 days ]
Overall response (OR) defined as either complete response (CR) or partial response (PR) observed in the first 3 treatment cycles. International Workshop Standardized Response Criteria for non-Hodgkin's Lymphoma used for measurable disease.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Akt/ERK Inhibitor ONC201 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title  ICMJE Phase I/II Study of Oral ONC201 in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Akt/ERK Inhibitor ONC201
    Given PO
    Other Names:
    • ONC201
    • TIC10
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacological Study
    Correlative studies
Study Arms  ICMJE 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.
Interventions:
  • Drug: Akt/ERK Inhibitor ONC201
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 19, 2020)
16
Original Estimated Enrollment  ICMJE
 (submitted: April 17, 2015)
60
Actual Study Completion Date  ICMJE November 16, 2020
Actual Primary Completion Date November 16, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02420795
Other Study ID Numbers  ICMJE 2014-0630
NCI-2015-00706 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
204666
20152142
1-909048-1
1159132
2014-0630 ( Other Identifier: M D Anderson Cancer Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Luhua (Michael) Wang M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP