A Phase I Open-Label Study of S-Trans, Trans-Farnesylthiosalicylic Acid (FTS) Administered on Days 1 to 21 of a 28 Day Cycle in Patients With Advanced Hematologic Malignancies
18 Years
N/A
Both
Myelodysplastic Syndrome, Leukemia
Trial Information
A Phase I Open-Label Study of S-Trans, Trans-Farnesylthiosalicylic Acid (FTS) Administered on Days 1 to 21 of a 28 Day Cycle in Patients With Advanced Hematologic Malignancies
FTS is designed to interfere with a cancer cell's ability to reproduce.
Before you can start receiving the drug on this study, you will have "screening tests."
These tests will help the doctor decide if you are eligible to take part in this study.
Your complete medical history will be recorded, and you will have a physical exam. You will
be asked about any side effects that you are having and about any medications that you are
taking. Your weight and vital signs (blood pressure, heart rate, breathing rate, and
temperature) will be measured. Blood (about 2 tablespoons) and urine will be collected for
routine tests. You will be asked about your ability to perform everyday tasks. You will
have an electrocardiogram (ECG - test to measure the electrical activity of the heart). A
bone marrow aspirate and/or biopsy will be collected to check the status of the disease. To
collect a bone marrow aspirate and/or biopsy, an area of the hip or chest bone is numbed
with anesthetic and a small amount (about 1 teaspoon) of bone marrow and bone is withdrawn
through a large needle. Women who are able to have children must have a negative blood
(about 1 tablespoon) or urine pregnancy test.
If you are found to be eligible for this study, you will take FTS by mouth, morning and
night with food, on Days 1-21 of a 28-day study "cycle."
The amount of study drug you will receive will be based on when you enter the study. At
least 3 participants will be taking FTS at the same dose level. Doses will be increased for
the next group of 3 participants based on the side effects seen in the previous group. Each
new group of participants will receive a higher dose level than the previous group, until a
level is reached where side effects are considered to be intolerable.
After each cycle, your doctor may decide to increase your dose if you are not having
intolerable side effects and you are benefitting from the study drug. If you experience
intolerable side effects during any of the cycles of therapy with FTS, your dose may be
reduced, delayed, or you may be taken off the study.
On Day 1 of the study, your weight and vital signs will be measured. Blood (about 1
tablespoon) will be collected for routine tests. You will not take your evening dose of FTS
on Day 1.
On Days 8,15, and 22 of the first cycle, your weight and vital signs will be measured. You
will be asked about any side effects that you are having, and about any medications that you
are taking. On Day 15 of Cycle 1, blood (about 1 tablespoon) will also be drawn for routine
tests.
During Cycle 1, on Days 1, 8, and 15, blood (about 1 tablespoon per draw) will be drawn to
find out how much drug there is in your blood at different time points. This will help
researchers to learn how FTS is processed by your body. This is called pharmacokinetic (PK)
testing. Blood will be drawn before your morning dose of FTS, at 30, 60, and 90 minutes
after taking the morning dose, and at 2, 4, 6, 8 and 24 hours after taking the morning dose.
During Cycle 1, on Days 1 and 15, blood (about 3 tablespoons per draw) will be drawn to
determine how FTS works against leukemia cells. This blood will be drawn before and 24
hours, after taking the morning dose on Day 1 and before you take the dose on Day 15.
On Day 1 of each cycle after Cycle 1, your weight and vital signs will be measured. Blood
(about 2 tablespoons) and urine will be collected for routine tests. You will be asked
about your ability to perform everyday tasks. You will be asked about any side effects that
you are having, and about any medications that you are taking.
On Days 8, 15, and 22 of every cycle after Cycle 1, you will be asked about any side effects
that you are having and about any medications that you are taking. On Day 15, blood (about
1 tablespoon) will also be drawn for routine tests, and your weight and vital signs will be
measured.
You may remain on study for as long as you are benefiting. You will be taken off study if
you are not benefitting or if you are experiencing intolerable side effects.
Thirty (30) days after you are no longer taking the study drug, you will have an
end-of-study visit. Blood (about 2 tablespoons) and urine will be collected for routine
tests. Your weight and vital signs will be measured. You will be asked about your ability
to perform everyday tasks. You will be asked about any side effects that you are having,
and about any medications that you are taking. You will have an ECG and an evaluation of
your disease, which may include a bone marrow aspiration and/or biopsy.
This is an investigational study. FTS is not FDA approved or commercially available, and it
has been authorized for use in research only. Up to 30 patients will take part in this
multicenter study. Up to 20 patients will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Patients must have relapsed/refractory hematologic malignancies for which no standard
therapies are anticipated to result in a durable response or who have failed
potentially curative therapy, or who refuse or are considered unsuitable for standard
therapy. Patients with poor-risk myelodysplastic syndromes (MDS) [IPSS ≥ 1.5],
chronic myelomonocytic leukemia (CMML), relapsed/refractory leukemias including
2. CONTINUATION OF # 1: acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL),
chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blastic
phase, or with agnogenic myeloid metaplasia (AMM) are eligible.
3. Patients are eligible if they are 18 years or older
4. 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
chronic clinically significant toxicities from prior chemotherapy must not be greater
than Grade 1
5. Patients with active CNS disease are included and will be treated concurrently with
intrathecal therapy
6. Patients must have ECOG performance status (PS) of 0 - 2
7. Have serum creatinine less than or equal to 2.0 mg/dl; total bilirubin less than or
equal to 2.0 mg/dl; ALT and/or AST no more than 3X the upper limit of normal range
unless abnormal parameter level is considered related to leukemia.
8. Patients must be willing and able to sign written informed consent and be able to
comply with the study protocol for the duration of the study
9. Females of childbearing potential and males are required to practice adequate
contraception or abstinence prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately
Exclusion Criteria:
1. Impaired cardiac function, including any one of the following: myocardial infarction
within the previous 3 months; symptomatic coronary insufficiency or heart block;
uncontrolled congestive heart failure; moderate or severe pulmonary dysfunction
2. Have an active uncontrolled infectious process
3. Significant impairment of gastrointestinal (GI) function of GI disease that may
significantly alter the absorption of FTS(e.g. ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
4. Have received prior radiotherapy administered to more than 30% of marrow-bearing bone
mass
5. Women patients are pregnant or lactating
6. Patients who have had major surgery without full recovery or major surgery within
three weeks of FTS treatment start
7. Patients with marked baseline prolongation of QT/QTc interval (QTc interval greater
than 480) using the Fridericia method as a main method of QTC analysis
8. Patients unwilling or unable to comply with the protocol
Type of Study:
Interventional
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)
Outcome Time Frame:
Continous assessment throughout study and determination of dose limiting toxicities with each 28 day cycle.
Safety Issue:
Yes
Principal Investigator
Gautam Borthakur, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2006-0201
NCT ID:
NCT00867230
Start Date:
May 2006
Completion Date:
February 2009
Related Keywords:
- Myelodysplastic Syndrome
- Leukemia
- Myelodysplastic Syndrome
- Chronic Myelomonocytic Leukemia
- Acute Myeloid Leukemia
- Acute Lymphocytic Leukemia
- Chronic Lymphocytic Leukemia
- Chronic Myelogenous Leukemia
- Agnogenic Myeloid Metaplasia
- FTS
- S-Trans, Trans-Farnesylthiosalicylic Acid
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
- Hematologic Neoplasms
Name | Location |
|---|---|
| U.T.M.D. Anderson Cancer Center | Houston, Texas 77030 |
