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ONC201 in Treating Patients With Relapsed or Refractory Acute Leukemia or High-Risk Myelodysplastic Syndrome

Primary Purpose

Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent Myelodysplastic Syndrome

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Akt/ERK Inhibitor ONC201
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • For Arms A, B, C, D, E patients must have relapsed or refractory acute leukemias or high-risk MDS for which no standard therapies are anticipated to result in a durable remission
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device, such as a condom, diaphragm, or cervical/vault cap), for 16 weeks after the last dose of study drug, and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial; nursing patients are excluded; sexually active men must also use acceptable contraceptive methods for the duration of time on study and for at least 16 weeks after the last dose of study drug; pregnant and nursing patients are excluded because the effects of ONC201on a fetus or nursing child are unknown
  • Must be able and willing to give written informed consent
  • The interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents; if the patient is on hydroxyurea to control peripheral blood leukemic cell counts, the patient must be off hydroxyurea for at least 24 hours before initiation of treatment on this protocol; persistent clinically significant toxicities from prior therapy must not be greater than grade 1
  • Serum creatinine < 2.0 mg/dl
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN) unless considered due to Gilbert's syndrome
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3 x the ULN unless considered due to organ leukemic involvement

  • Relapse > 6 months since autologous or allogeneic stem cell transplantation provided:

    • No active graft-versus-host disease (GVHD > grade 1)
    • No treatment with high dose steroids for GVHD (up to >= 20 mg prednisolone or equivalent per day)
    • No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (New York Heart Association class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure (New York Heart Association class III and IV)
  • Patients receiving any other standard or investigational treatment for their hematologic malignancy within past 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents
  • Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy
  • Known history of seropositive for human immunodeficiency virus (HIV) antibodies (HIV1 and HIV2), hepatitis C antibody (Hep C Ab) or a hepatitis B carrier (positive for hepatitis B surface antigen [HBsAg])
  • Active drug use or alcoholism
  • Known or active central nervous system (CNS) involvement by leukemia
  • Concomitant use of strong CYP3A inhibitors

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm A (Akt/ERK inhibitor ONC201)

Arm B (Akt/ERK inhibitor ONC201)

Arm C (Akt/ERK inhibitor ONC201)

Arm D (Akt/ERK inhibitor ONC201)

Arm E (Akt/ERK inhibitor ONC201)

Arm Description

Patients receive Akt/ERK inhibitor ONC201 PO once every 3 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive Akt/ERK inhibitor ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive Akt/ERK inhibitor ONC201 PO on the first two consecutive days of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive Akt/ERK inhibitor ONC201 PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive Akt/ERK inhibitor ONC201 PO twice weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of ONOC201 in Relapsed or Refractory Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS) or Acute Lymphoblastic Leukemia (ALL)
MTD is defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT). Toxicities defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DLT defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first cycle on study that meets any of the following criteria: CTCAE grade 3 AST (SGOT) or ALT (SGPT) for > 7 days CTCAE grade 4 AST (SGOT) or ALT (SGPT) of any duration All other clinically significant NCI common terminology criteria that are CTCAE grade 3 or 4 (except for electrolyte disturbances responsive to correction within 24 h, diarrhea, nausea and vomiting that responds to standard medical care)
Objective Response (OR) (Phase II)
Objective responses for patients with AML and ALL include Complete Remission (CR), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) and morphologic leukemia-free state(Cheson and others, 2003).

Secondary Outcome Measures

Full Information

First Posted
March 13, 2015
Last Updated
October 2, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
Oncoceutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02392572
Brief Title
ONC201 in Treating Patients With Relapsed or Refractory Acute Leukemia or High-Risk Myelodysplastic Syndrome
Official Title
Phase I/II Study of Oral ONC201 in Patients With Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2015 (Actual)
Primary Completion Date
November 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
Oncoceutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This phase I/II trial studies the side effects and best dose of ONC201 and to see how well it works in treating patients with acute leukemia or high-risk myelodysplastic syndrome that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). 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) alone in patients with relapsed or refractory acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) or acute lymphoblastic leukemia (ALL). (Phase I) II. To identify toxicities associated with oral ONC201 alone in patients with relapsed or refractory AML, MDS or ALL. (Phase I) III. To determine the objective response rate to ONC201 alone in patients with relapsed or refractory AML, MDS or ALL. (Phase II) SECONDARY OBJECTIVES: I. To determine the pharmacokinetics (PK) of oral ONC201 alone. (Phase I) II. To observe the anti-tumor effects of oral ONC201 alone in patients with relapsed or refractory AML, MDS or ALL. (Phase I) III. Confirm tolerability of recommended phase II dose. (Phase II) IV. Assess clinical outcomes associated with ONC201 alone in patients with relapsed or refractory AML, MDS or ALL. (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 are assigned to 1 of 5 arms. ARM A: Patients receive Akt/ERK inhibitor ONC201 orally (PO) once every 3 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive Akt/ERK inhibitor ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive Akt/ERK inhibitor ONC201 PO on the first two consecutive days of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM D: Patients receive Akt/ERK inhibitor ONC201 PO once daily (QD). Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM E: Patients receive Akt/ERK inhibitor ONC201 PO twice weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 28 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Myeloid Leukemia, Refractory Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (Akt/ERK inhibitor ONC201)
Arm Type
Experimental
Arm Description
Patients receive Akt/ERK inhibitor ONC201 PO once every 3 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm B (Akt/ERK inhibitor ONC201)
Arm Type
Experimental
Arm Description
Patients receive Akt/ERK inhibitor ONC201 PO once every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm C (Akt/ERK inhibitor ONC201)
Arm Type
Experimental
Arm Description
Patients receive Akt/ERK inhibitor ONC201 PO on the first two consecutive days of every week. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm D (Akt/ERK inhibitor ONC201)
Arm Type
Experimental
Arm Description
Patients receive Akt/ERK inhibitor ONC201 PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm E (Akt/ERK inhibitor ONC201)
Arm Type
Experimental
Arm Description
Patients receive Akt/ERK inhibitor ONC201 PO twice weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Akt/ERK Inhibitor ONC201
Other Intervention Name(s)
ONC-201, ONC201, TIC10
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of ONOC201 in Relapsed or Refractory Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS) or Acute Lymphoblastic Leukemia (ALL)
Description
MTD is defined as the highest dose level in which 6 patients have been treated with at most 1 instance of dose limiting toxicity (DLT). Toxicities defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. DLT defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first cycle on study that meets any of the following criteria: CTCAE grade 3 AST (SGOT) or ALT (SGPT) for > 7 days CTCAE grade 4 AST (SGOT) or ALT (SGPT) of any duration All other clinically significant NCI common terminology criteria that are CTCAE grade 3 or 4 (except for electrolyte disturbances responsive to correction within 24 h, diarrhea, nausea and vomiting that responds to standard medical care)
Time Frame
21 days
Title
Objective Response (OR) (Phase II)
Description
Objective responses for patients with AML and ALL include Complete Remission (CR), Complete Remission with Incomplete Blood Count Recovery (CRi), Partial Remission (PR) and morphologic leukemia-free state(Cheson and others, 2003).
Time Frame
63 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: For Arms A, B, C, D, E patients must have relapsed or refractory acute leukemias or high-risk MDS for which no standard therapies are anticipated to result in a durable remission Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device, such as a condom, diaphragm, or cervical/vault cap), for 16 weeks after the last dose of study drug, and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial; nursing patients are excluded; sexually active men must also use acceptable contraceptive methods for the duration of time on study and for at least 16 weeks after the last dose of study drug; pregnant and nursing patients are excluded because the effects of ONC201on a fetus or nursing child are unknown Must be able and willing to give written informed consent The interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents; if the patient is on hydroxyurea to control peripheral blood leukemic cell counts, the patient must be off hydroxyurea for at least 24 hours before initiation of treatment on this protocol; persistent clinically significant toxicities from prior therapy must not be greater than grade 1 Serum creatinine < 2.0 mg/dl Total bilirubin =< 1.5 x the upper limit of normal (ULN) unless considered due to Gilbert's syndrome Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3 x the ULN unless considered due to organ leukemic involvement Relapse > 6 months since autologous or allogeneic stem cell transplantation provided: No active graft-versus-host disease (GVHD > grade 1) No treatment with high dose steroids for GVHD (up to >= 20 mg prednisolone or equivalent per day) No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus Exclusion Criteria: Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure (New York Heart Association class III and IV), uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure (New York Heart Association class III and IV) Patients receiving any other standard or investigational treatment for their hematologic malignancy within past 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy Known history of seropositive for human immunodeficiency virus (HIV) antibodies (HIV1 and HIV2), hepatitis C antibody (Hep C Ab) or a hepatitis B carrier (positive for hepatitis B surface antigen [HBsAg]) Active drug use or alcoholism Known or active central nervous system (CNS) involvement by leukemia Concomitant use of strong CYP3A inhibitors
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gautam Borthakur
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gautam Borthakur
Phone
713-563-1586
First Name & Middle Initial & Last Name & Degree
Gautam Borthakur

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center

Learn more about this trial

ONC201 in Treating Patients With Relapsed or Refractory Acute Leukemia or High-Risk Myelodysplastic Syndrome

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