4'-Thio-araC (Thiarabine) in Advanced Hematologic Malignancies

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. Identifier: NCT01139151
Recruitment Status : Completed
First Posted : June 8, 2010
Last Update Posted : June 17, 2014
Access Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to find the highest tolerable dose of 4'-thio-araC (thiarabine) that can be given to patients with advanced blood cancer. The safety of this drug will also be studied and 2 different dose schedules will be tested.

Condition or disease Intervention/treatment Phase
Leukemia Drug: 3 Day Thiarabine Drug: 5 Day Thiarabine Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies
Study Start Date : August 2010
Actual Primary Completion Date : November 2011
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: Group 1 - 3 Day Thiarabine
Thiarabine 3 days in a row in each cycle.
Drug: 3 Day Thiarabine
Starting dose 70 mg/m^2 IV over 1 hour (±15 minutes) daily x 3
Other Name: 4'-Thio-araC
Experimental: Group 2 - 5 Day Thiarabine
Thiarabine 5 days a row in each cycle.
Drug: 5 Day Thiarabine
Starting dose 40 mg/m2 IV over 1 hour (±15 minutes) daily x 5
Other Name: 4'-Thio-araC

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of 4'-thio-araC [ Time Frame: 3 weeks ]
    The MTD is the highest dose level in which <2 patients of six develop first cycle dose-limiting toxicity (DLT).

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Patients with poor-risk myelodysplasia (MDS) [i.e. refractory anemia with excess blasts (RAEB-1 or RAEB-2) by WHO classification] and chronic myelomonocytic leukemia (CMML) are also candidates for this protocol. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML) by WHO classification, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis.
  2. Patients with refractory/relapsed leukemia 16 years or older are eligible. Patients 60 years or older with newly diagnosed AML are eligible if they are not candidates for, or if they refuse, intensive chemotherapy.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
  4. Women of child-bearing potential (ie, a woman who has not been postmenopausal for at least 12 consecutive months or who had not undergone previous surgical sterilization) must use acceptable contraceptive methods (abstinence, intrauterine device (IUD), oral contraceptive or double barrier device), and must have a negative urine pregnancy test within 2 weeks 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.
  5. Continued from #4: Pregnant and nursing patients are excluded because the effects of 4'-thio-araC on a fetus or nursing child are unknown.
  6. Must be able and willing to give written informed consent
  7. In the absence of rapidly progressing disease, 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 chemotherapy must not be greater than grade 1.
  8. Patients must have the following clinical laboratory values unless considered due to leukemic organ involvement: 1. Serum creatinine </= 1.3 mg/dl or creatinine clearance > 40 ml/min. 2. Total bilirubin </= 1.5* the upper limit of normal unless considered due to Gilbert's syndrome. 3. Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) </= 3* the upper limit of normal unless considered due to organ leukemic involvement.
  9. Patients with active central nervous system (CNS) involvement of leukemia disease are included and will be treated concurrently with intrathecal therapy.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness including, but not limited to uncontrolled infection (e.g. requiring IV antibiotics, etc), symptomatic congestive heart failure, 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, corrected QT interval (QTc) > 480, arrhythmias not controlled by medication, or uncontrolled congestive heart failure defined as Class II to IV per New York Heart Association Classification.
  3. Patients receiving any other standard or investigational treatment for their hematologic malignancy.
  4. Patients with known HIV positive disease; patients with active hepatitis.

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 identifier (NCT number): NCT01139151

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Access Pharmaceuticals, Inc.
Study Chair: Hagop Kantarjian, MD UT MD Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01139151     History of Changes
Other Study ID Numbers: 2009-1000
NCI-2012-01785 ( Registry Identifier: NCI CTRP )
First Posted: June 8, 2010    Key Record Dates
Last Update Posted: June 17, 2014
Last Verified: June 2014

Keywords provided by M.D. Anderson Cancer Center:
Advanced Hematologic Malignancies
deoxycytidine nucleoside analog
poor-risk myelodysplasia
refractory anemia
Excess blasts
Chronic myelomonocytic leukemia
Relapsed/refractory leukemia
Acute non-lymphocytic leukemia
Acute lymphocytic leukemia
Chronic lymphocytic leukemia
Chronic myelogenous leukemia
blast crisis

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs