LeukemiaPhase 1NCT01139151
4'-Thio-araC (Thiarabine) in Advanced Hematologic Malignancies
A Phase 1 study testing 3 Day Thiarabine and 5 Day Thiarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- 3 Day Thiarabine and 5 Day Thiarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Nov 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies
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.
Read the detailed description
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.
Follow-Up:
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.
- Conditions
- Leukemia
- Being tested
- 3 Day Thiarabine, 5 Day Thiarabine
- 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
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3 Day ThiarabineDrug
Also called 4'-Thio-araC
Starting dose 70 mg/m^2 IV over 1 hour (±15 minutes) daily x 3
5 Day ThiarabineDrug
Also called 4'-Thio-araC
Starting dose 40 mg/m2 IV over 1 hour (±15 minutes) daily x 5
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - 3 Day Thiarabine | Experimental | Thiarabine 3 days in a row in each cycle. Receives: Drug: 3 Day Thiarabine |
| Group 2 - 5 Day Thiarabine | Experimental | Thiarabine 5 days a row in each cycle. Receives: Drug: 5 Day Thiarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2010 (estimated)
- Study startAug 2010
- Primary completionNov 2011
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Access Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Hagop Kantarjian, MD, Study chair, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01139151
- Sponsor's protocol ID
- 2009-1000
- Other IDs
- NCI-2012-01785
- Status last verified
- Jun 2014
- First submitted
- 4 Jun 2010
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of 4'-Thio-araC in Patients With Advanced Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01139151
- Acronym / sponsor ID
- 2009-1000
- Conditions
- Leukemia
- Keywords
- Advanced Hematologic Malignancies, 4'-Thio-araC, Thiarabine, 4'-thio-â-D-arabinofuranosylcytosine, deoxycytidine nucleoside analog, poor-risk myelodysplasia, MDS, refractory anemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Access Pharmaceuticals, Inc.
- Study start
- Aug 2010
- Primary completion
- Nov 2011 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 8 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Follow-Up:
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - 3 Day Thiarabine | Experimental | Drug: 3 Day ThiarabineThiarabine 3 days in a row in each cycle. |
| Group 2 - 5 Day Thiarabine | Experimental | Drug: 5 Day ThiarabineThiarabine 5 days a row in each cycle. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3 Day ThiarabineAlso: 4'-Thio-araCStarting dose 70 mg/m^2 IV over 1 hour (±15 minutes) daily x 3 | Drug | Group 1 - 3 Day Thiarabine |
| 5 Day ThiarabineAlso: 4'-Thio-araCStarting dose 40 mg/m2 IV over 1 hour (±15 minutes) daily x 5 | Drug | Group 2 - 5 Day Thiarabine |
Primary outcome
Maximum Tolerated Dose (MTD) of 4'-thio-araC
Time frame: 3 weeks
The MTD is the highest dose level in which <2 patients of six develop first cycle dose-limiting toxicity (DLT).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2014.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hagop Kantarjian, MD study chair
UT MD Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 3 Day Thiarabine and 5 Day Thiarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of 4'-thio-araC (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2014.