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ONC201 in Relapsed/Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes (HR-MDS)

This study is currently recruiting participants.
Verified June 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT02392572
First Posted: March 19, 2015
Last Update Posted: June 9, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Oncoceutics, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

The goal of Phase I of this clinical research study is to find the highest tolerable dose of ONC201 that can be given to patients with relapsed or refractory AML, ALL, or MDS.

The goal of Phase II of this study is to learn if the dose of ONC201 found in Phase I can help to control the disease. The safety of the study drug will be studied in both phases of this study. This is the first study using ONC201 in humans. ONC201 is in a very early stage of development for use in humans. Providing direct medical benefit to you is not the purpose of this study. While Phase II will look at the effectiveness of the study drug, the main purpose of this study is to learn about the safety of the drug.


Condition Intervention Phase
Leukemia Drug: ONC201 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Oral ONC201 in Patients With Relapsed or Refractory Acute Leukemias and High-Risk Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

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) [ Time Frame: 21 days ]

    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)


Secondary Outcome Measures:
  • Objective Response (OR) [ Time Frame: 63 days ]
    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).


Estimated Enrollment: 120
Actual Study Start Date: November 2015
Estimated Study Completion Date: November 2022
Estimated Primary Completion Date: November 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Relapsed or Refractory Acute Myelogenous Leukemia (AML)

ONC201 dosed orally once every three weeks. One cycle defined as 21 days (3 weeks).

Phase I: Cohorts consisting of one new patient per dosing level treated sequentially at rising dose levels starting at 125 mg. Enrollment at each dose level requires that all patients enrolled at the prior dose level have completed one cycle of treatment (21 days) and that dose level is deemed safe. Dose escalation continues until an maximum tolerated dose (MTD) is reached or dose level 5 is reached (625 mg), which will be declared the maximum administered dose (MAD).

Phase II: Starting dose is MTD dose from Phase I.

Drug: ONC201

Phase I Starting dose of ONC201: 125 mg by mouth once every 3 weeks.

Phase II Starting dose of ONC201: MTD from Phase I.

Experimental: Myelodysplastic Syndrome (MDS)

ONC201 dosed orally once every 1 week. One cycle defined as 21 days (3 weeks).

Phase I: Cohorts consisting of one new patient per dosing level treated sequentially at rising dose levels starting at 125 mg. Enrollment at each dose level requires that all patients enrolled at the prior dose level have completed one cycle of treatment (21 days) and that dose level is deemed safe. Dose escalation continues until an maximum tolerated dose (MTD) is reached or dose level 5 is reached (625 mg), which will be declared the maximum administered dose (MAD).

Phase II: Starting dose is MTD dose from Phase I.

Drug: ONC201

Phase I Starting dose of ONC201: 125 mg by mouth once every 3 weeks.

Phase II Starting dose of ONC201: MTD from Phase I.

Experimental: Acute Lymphoblastic Leukemia (ALL).

ONC201 dosed orally on the first two consecutive days of every week. One cycle defined as 21 days (3 weeks).

Phase I: Cohorts consisting of one new patient per dosing level treated sequentially at rising dose levels starting at 125 mg. Enrollment at each dose level requires that all patients enrolled at the prior dose level have completed one cycle of treatment (21 days) and that dose level is deemed safe. Dose escalation continues until an maximum tolerated dose (MTD) is reached or dose level 5 is reached (625 mg), which will be declared the maximum administered dose (MAD).

Phase II: Starting dose is MTD dose from Phase I.

Drug: ONC201

Phase I Starting dose of ONC201: 125 mg by mouth once every 3 weeks.

Phase II Starting dose of ONC201: MTD from Phase I.


  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age >/=18 years.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  4. 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.
  5. Must be able and willing to give written informed consent.
  6. 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.
  7. Patients must have the following clinical laboratory values unless considered due to leukemic organ involvement: (1) Serum creatinine < 2.0 mg/dl; (2) Total bilirubin </= 1.5 x the upper limit of normal (ULN) unless considered due to Gilbert's syndrome; (3) Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) </= 3 x the ULN unless considered due to organ leukemic involvement.
  8. Patients with known central nervous system (CNS) disease are allowed if there is no evidence of active CNS disease as documented by negative imaging or spinal fluid analysis carried out at least 2 weeks prior to study drug administration. Information obtained from standard of care historical data will be used for this purpose.
  9. Relapse > 6 months since autologous or allogeneic stem cell transplantation provided: (1) No active graft-versus-host disease (GVHD > grade 1); (2) No treatment with high dose steroids for GVHD (up to >/= 20 mg Prednisolone or equivalent per day); (3) No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus.

Exclusion Criteria:

  1. 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.
  2. 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).
  3. 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.
  4. 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.
  5. 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])
  6. Active drug use or alcoholism.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02392572


Contacts
Contact: Gautam Borthakur, MBBS 713-563-1586

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Oncoceutics, Inc.
Investigators
Principal Investigator: Gautam Borthakur, MBBS M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02392572     History of Changes
Other Study ID Numbers: 2014-0731
NCI-2015-00504 ( Registry Identifier: NCI CTRP )
First Submitted: March 13, 2015
First Posted: March 19, 2015
Last Update Posted: June 9, 2017
Last Verified: June 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute myelogenous leukemia
AML
Myelodysplastic syndrome
MDS
Acute lymphoblastic leukemia
ALL
Relapsed
Refractory
ONC201

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions