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

NCT01139151 | Completed Phase 1

• 2 other identifiers: 2009-1000NCI-2012-01785
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of 4'-thio-araC

  The MTD is the highest dose level in which \<2 patients of six develop first cycle dose-limiting toxicity (DLT).

  3 weeks

Study Arms (2)

Group 1 - 3 Day Thiarabine

EXPERIMENTAL

Thiarabine 3 days in a row in each cycle.

Drug: 3 Day Thiarabine

Group 2 - 5 Day Thiarabine

EXPERIMENTAL

Thiarabine 5 days a row in each cycle.

Drug: 5 Day Thiarabine

Interventions

3 Day Thiarabine DRUG

Starting dose 70 mg/m\^2 IV over 1 hour (±15 minutes) daily x 3

Also known as: 4'-Thio-araC

Group 1 - 3 Day Thiarabine

5 Day Thiarabine DRUG

Starting dose 40 mg/m2 IV over 1 hour (±15 minutes) daily x 5

Also known as: 4'-Thio-araC

Group 2 - 5 Day Thiarabine

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3.
• 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.
• Continued from #4: Pregnant and nursing patients are excluded because the effects of 4'-thio-araC on a fetus or nursing child are unknown.
• Must be able and willing to give written informed consent
• 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.
• 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.
• Patients with active central nervous system (CNS) involvement of leukemia disease are included and will be treated concurrently with intrathecal therapy.

You may not qualify if:

• 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.
• 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.
• Patients receiving any other standard or investigational treatment for their hematologic malignancy.
• Patients with known HIV positive disease; patients with active hepatitis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Access Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Anemia, Refractory; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis

Interventions

4'-thio-arabinofuranosylcytosine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Myeloproliferative Disorders; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Study Officials

• Hagop Kantarjian, MD

  UT MD Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2010
• First Posted: June 8, 2010
• Study Start: August 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2013
• Last Updated: June 17, 2014

Record last verified: 2014-06

Locations

US (1)