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Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies

Phase 1
16 Years
Open (Enrolling)

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Trial Information

Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies

The Study Drug:

Thiarabine is designed to damage and destroy the DNA of cancer cells. This may cause the
cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2
study groups based on when you joined the study. The first set of 3 participants will be
enrolled in Group 1, and the 2nd set of 3 participants will be enrolled in Group 2. The 3rd
set of 3 participants will be enrolled in Group 1, then the 4th set of 3 participants in
Group 2, and so on until all participants are enrolled.

- Group 1 will receive thiarabine for 3 days in a row in each cycle.

- Group 2 will receive thiarabine for 5 days a row in each cycle.

Cycles in this study are 3-6 weeks long, depending on how you are doing. You may begin a
new cycle when your blood cell counts have returned to an appropriate level. However, you
may begin a new study cycle earlier than that if the disease gets worse or does not improve.

The dose of thiarabine you receive will depend on when you joined this study. The first set
of participants will receive the lowest dose level of thiarabine. Each new set will receive
a higher dose of thiarabine than the set before it, if no intolerable side effects were
seen. This will continue until the highest tolerable dose of thiarabine is found.

Study Drug Administration:

You will receive thiarabine by vein over about 1 hour (+/- 15 minutes) on Days 1-3 (Group 1)
or Days 1-5 (Group 2) of each cycle.

Study Visits:

Blood (about 2 tablespoons) will be drawn for routine tests 1 or 2 times a week. If the
disease responds well, the study doctor may decide these blood tests will occur less often.

At every study visit, you will be asked about any drugs you may be taking and symptoms you
may be having.

You will have an ECG within 2 days before each cycle.

At any time the doctor thinks it is needed, you will have a bone marrow aspiration to check
the status of the disease.

Length of Participation:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. You will be taken off study early if intolerable side effects occur. You may be
taken off study early if the disease gets worse.


At 30 days after your last study drug dose, you will be asked about any side effects you may
be having. This may be done during a regular clinic visit or by phone call from the study
doctor or staff.

This is an investigational study. Thiarabine is not FDA approved or commercially available.
It is currently being used for research purposes only.

Up to 70 patients will take part in this study. All will be enrolled at MD Anderson.

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 > 40 ml/min. 2. Total bilirubin due to Gilbert's syndrome. 3. Alanine aminotransferase (ALT), or aspartate
aminotransferase (AST) 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, 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Hagop Kantarjian, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

Related Keywords:

  • Leukemia
  • Advanced Hematologic Malignancies
  • 4'-Thio-araC
  • Thiarabine
  • 4'-thio-รข-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
  • Neoplasms
  • Leukemia
  • Hematologic Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030