FTS Study in Patients With Advanced Hematologic Malignancies

July 31, 2012 updated by: M.D. Anderson Cancer Center

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

Primary Objective:

Determining the maximum tolerated dose (MTD) and pharmacokinetics (PK) of FTS (S-Trans, Trans-Farnesylthiosalicylic Acid) after daily oral administration on Days 1 through 21 of a 28-Day cycle to patients with advanced hematologic malignancies that have progressed following effective therapy or for which no effective therapy exists.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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of the hip or chest bone is numbed with anesthetic and a small amount (about 1 teaspoon) of bone marrow and bone is withdrawn through a large needle.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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • U.T.M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FTS (S-trans, trans-farnesylthiosalicylic acid)
Drug: FTS
Starting dose of 100 mg twice a day by mouth, Days 1 through 21 of a 28-day cycle.
Other Names:
  • S-trans, trans-farnesylthiosalicylic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: Continous assessment throughout study and determination of dose limiting toxicities with each 28 day cycle.
Continous assessment throughout study and determination of dose limiting toxicities with each 28 day cycle.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Concordia Pharmaceuticals, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2006

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

March 20, 2009

First Submitted That Met QC Criteria

March 20, 2009

First Posted (Estimate)

March 23, 2009

Study Record Updates

Last Update Posted (Estimate)

August 1, 2012

Last Update Submitted That Met QC Criteria

July 31, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006-0201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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