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

This study has been completed.
Sponsor:
Collaborator:
Access Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01139151
First received: June 4, 2010
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Leukemia
Drug: 3 Day Thiarabine
Drug: 5 Day Thiarabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies

Resource links provided by NLM:


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

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


Enrollment: 31
Study Start Date: August 2010
Study Completion Date: November 2013
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01139151

Locations
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.
Investigators
Study Chair: Hagop Kantarjian, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01139151     History of Changes
Other Study ID Numbers: 2009-1000, NCI-2012-01785
Study First Received: June 4, 2010
Last Updated: June 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Hematologic Malignancies
4'-Thio-araC
Thiarabine
4'-thio-â-D-arabinofuranosylcytosine
deoxycytidine nucleoside analog
poor-risk myelodysplasia
MDS
refractory anemia
Excess blasts
RAEB-1
RAEB-2
Chronic myelomonocytic leukemia
CMML
Relapsed/refractory leukemia
Acute non-lymphocytic leukemia
AML
Acute lymphocytic leukemia
ALL
Chronic lymphocytic leukemia
CLL
Chronic myelogenous leukemia
CML
blast crisis

Additional relevant MeSH terms:
Neoplasms
Leukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Hematologic Diseases
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014