Acute LeukemiaPhase 1NCT00592046
A Phase I Trial of ZIO-101 in Hematologic Cancers
A Phase 1 study testing ZIO-101 (Darinaparsin) in people with Acute Leukemia and Chronic Myeloproliferative Disease, run by Alaunos Therapeutics at 1 site in United States.
Trial summary
This study uses a new investigational (not yet approved by the FDA for widespread use) drug called ZIO-101, an organic arsenical. You must be diagnosed to have relapsed/refractory leukemia or lymphoma (blood cancer) and have tried other standard therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Leukemia, Chronic Myeloproliferative Disease, Chronic Lymphoproliferative Disease
- What is being tested?
- ZIO-101 (Darinaparsin)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jun 2008
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have relapsed/refractory leukemia or lymphoma for which no standard therapies are anticipated to result in a durable remission. Relapsed/refractory leukemia/lymphoma includes acute leukemia, chronic myeloproliferative disease, chronic lymphoproliferative disease, multiple myeloma, and any type of lymphoma. Subjects with poor-risk myelodysplasia (MDS) are also candidates for this protocol. Poor risk MDS includes refractory anemia with excess blasts or excess blasts in transformation, and chronic myelomonocytic leukemia.
- ECOG performance status of ≤ 2.
- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing subjects are excluded. Sexually active men must also use acceptable contraceptive methods. Pregnant and nursing subjects are excluded because the effects of ZIO-101 on a fetus or nursing child are unknown.
- Must be able and willing to give written informed consent.
- Absent rapidly progressing disease, the interval from cancer therapy should be ≥ 3 weeks. Subjects receiving hydroxyurea should be on stable dose ≥ 7 days before beginning treatment protocol. Persisting chronic toxicities from prior therapy must be ≤ grade 1.
- Subjects must have the following clinical laboratory values:
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- Serum creatinine ≤ 2 x the upper limit of normal
- Total bilirubin ≤ 2 x the upper limit of normal.
- Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) ≤ 3 x the upper limit of normal.
- QTc interval < 450-470 mSec
Who cannot join
- Subjects with any one of the following criteria will not be eligible for study participation:
- Patients with indolent and stable myeloma, MDS or CLL not requiring therapy are not eligible.
- Central nervous system (CNS) involvement with cancer.
- Uncontrolled active infection of any kind. Subjects with infections that are under active treatment with antibiotics and whose infections are controlled may be entered to the study.
- Active heart disease including myocardial infarction within previous 6 months; symptomatic coronary artery disease; any type of chronic, ongoing arrhythmias; or uncontrolled congestive heart failure.
- Concomitant therapy for hematologic cancer (except hydroxyurea).
- NYHA functional class ≥ 3, myocardial infarction ≤ 6 mo or uncontrolled cardiac arrhythmia other than asymptomatic atrial fibrillation; QTc ≥450msec; AV-block ≥ grade-2 or Left Bundle Branch Block.
Trial locations and contacts
1 site in 1 country.
About this study
This study uses a new investigational (not yet approved by the FDA for widespread use) drug called ZIO-101, an organic arsenical. You must be diagnosed to have relapsed/refractory leukemia or lymphoma (blood cancer) and have tried other standard therapies.
This study is designed to determine whether ZIO-101 may be given safely. The study will also test whether ZIO-101 helps to treat blood cancer.
Read more
We anticipate that approximately 22 to 35 patients will take part in this study.
Arsenic has been used as a medicinal agent for centuries in many different cultures. Most recently in the United States, an inorganic arsenic compound was approved by the FDA for the treatment of patients with relapsed acute promyelocytic leukemia (APL). However, use of inorganic arsenic is limited by a narrow range of activity and systemic toxicity, most notably of the cardiac system.
ZIO-101 is an organic arsenic derivative. In vitro testing in both the National Cancer Institute (NCI) cancer cell panel and in vivo testing in a leukemia animal model demonstrated substantial activity of SGLU against hematologic cancers. In vitro testing of SGLU using the NCI human cancer cell panel also detected activity against lung, colon and brain cancers, melanoma, and ovary and kidney cancers. Moderate activity was seen against breast and prostate cancers cells. Data suggest that organic arsenic generates reactive oxygen species in the cells to induce apoptosis and cell cycle arrest.
Read the detailed description
The purpose of this study is to find answers to the following questions:
- What is the largest dose of ZIO-101 that can be given once a day for 5 days every 4 weeks (a "cycle")?
- What are the side effects of ZIO-101 when administered in this way?
- After getting the drug how much of the ZIO-101 remains in the blood stream up to 8 days after the first injection?
- Is ZIO-101 useful in reducing my blood cancer?
A series of tests will be taken throughout the study: medical history will be recorded, a physical exam performed, an electrocardiogram (EKG) (a measurement of your heart activity), blood tests. The amount of blood taken for these lab tests will equal about 2 1/2 tablespoons. In addition, a urine pregnancy test (if applicable), and a urine sample taken to test if your kidneys are working correctly. To see the current condition of your blood cancer, additional tests may need to be performed if they have not already been done recently. These tests may include: a bone marrow biopsy, special testing of your blood, a CT scan and a bone scan.
Immediately before being treated with ZIO-101, you will have another physical examination, you will also be asked about any medicines you are taking and how you are feeling. The blood tests may need to be repeated along with the EKG and the urine test. In addition, a small blood sample must be taken immediately before the injection of ZIO-101.
The injections of ZIO-101 will take approximately one hour. Following the first injection only, you will have 6 samples of blood taken at 0.5, 1, 2, 4, 8 and 12 hours. Additional blood samples will be taken prior to each dose of ZIO-101 only. You will also have repeat EKG within one hour after completing the injection. This process will be repeated for 5 consecutive days.
Your next visit will be Week 2 and at the onset of this visit, a blood sample will be taken and you will be asked how you feel. At Weeks 3 and 4, another blood sample will be taken and you will be asked how you feel.
At the end of Week 4, a new cycle begins. Immediately before being treated with ZIO-101, you will have a physical examination, you will be asked about any medicines you are taking and how you are feeling. The blood tests will be repeated along with the EKG and the urine test. In addition, any test used to measure your blood cancer will be repeated toward the end of the cycle.
You may receive up to six of these cycles.
- Conditions
- Acute Leukemia, Chronic Myeloproliferative Disease, Chronic Lymphoproliferative Disease, Multiple Myeloma, Lymphoma, Poor-risk Myelodysplasia (MDS)
- Being tested
- ZIO-101 (Darinaparsin)
- Keywords
- Phase I, Hematologic Cancers, Blood Cancers, Leukemia, multiple myeloma, myelodysplasia (MDS), Relapsed/refractory leukemia or lymphoma
- Medical subject headings
- Myeloproliferative Disorders, Multiple Myeloma, Lymphoma, Hematologic Neoplasms, Leukemia, Anemia, Refractory, with Excess of Blasts, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZIO-101 (Darinaparsin)Drug
Also called ZIO-101
ZIO-101 (Darinaparsin) given for five consecutive days to be repeated every 28 days for up to six months. This is a dose escalation study.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Not described Receives: Drug: ZIO-101 (Darinaparsin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Measured: 6 months
Secondary outcomes (3)
The RECIST criteria will be used for patients with all leukemias and myelodysplastic syndromes.
Measured: 6 months
Patients with lymphoma or myeloma will be assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas.
Measured: 6 months
EBMT, IBMTR and ABMTR criteria for definition of response, relapse and progression in patients with multiple myeloma .
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2008 (estimated)
- Study startMay 2005
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- 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
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alaunos Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00592046
- Sponsor's protocol ID
- SGL1001
- Status last verified
- Jul 2012
- First submitted
- 26 Dec 2007
- Last updated
- 19 Jul 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of ZIO-101 in Hematologic Cancers
- ClinicalTrials.gov ID
- NCT00592046
- Acronym / sponsor ID
- SGL1001
- Conditions
- Acute Leukemia, Chronic Myeloproliferative Disease, Chronic Lymphoproliferative Disease, Multiple Myeloma, Lymphoma, Poor-risk Myelodysplasia (MDS)
- Keywords
- Phase I, Hematologic Cancers, Blood Cancers, Leukemia, multiple myeloma, myelodysplasia (MDS), Relapsed/refractory leukemia or lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Alaunos TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- May 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 11 Jan 2008 (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.
This study uses a new investigational (not yet approved by the FDA for widespread use) drug called ZIO-101, an organic arsenical. You must be diagnosed to have relapsed/refractory leukemia or lymphoma (blood cancer) and have tried other standard therapies.
This study is designed to determine whether ZIO-101 may be given safely. The study will also test whether ZIO-101 helps to treat blood cancer.
We anticipate that approximately 22 to 35 patients will take part in this study.
Arsenic has been used as a medicinal agent for centuries in many different cultures. Most recently in the United States, an inorganic arsenic compound was approved by the FDA for the treatment of patients with relapsed acute promyelocytic leukemia (APL). However, use of inorganic arsenic is limited by a narrow range of activity and systemic toxicity, most notably of the cardiac system.
ZIO-101 is an organic arsenic derivative. In vitro testing in both the National Cancer Institute (NCI) cancer cell panel and in vivo testing in a leukemia animal model demonstrated substantial activity of SGLU against hematologic cancers. In vitro testing of SGLU using the NCI human cancer cell panel also detected activity against lung, colon and brain cancers, melanoma, and ovary and kidney cancers. Moderate activity was seen against breast and prostate cancers cells. Data suggest that organic arsenic generates reactive oxygen species in the cells to induce apoptosis and cell cycle arrest.
Detailed description
The purpose of this study is to find answers to the following questions:
- What is the largest dose of ZIO-101 that can be given once a day for 5 days every 4 weeks (a "cycle")?
- What are the side effects of ZIO-101 when administered in this way?
- After getting the drug how much of the ZIO-101 remains in the blood stream up to 8 days after the first injection?
- Is ZIO-101 useful in reducing my blood cancer?
A series of tests will be taken throughout the study: medical history will be recorded, a physical exam performed, an electrocardiogram (EKG) (a measurement of your heart activity), blood tests. The amount of blood taken for these lab tests will equal about 2 1/2 tablespoons. In addition, a urine pregnancy test (if applicable), and a urine sample taken to test if your kidneys are working correctly. To see the current condition of your blood cancer, additional tests may need to be performed if they have not already been done recently. These tests may include: a bone marrow biopsy, special testing of your blood, a CT scan and a bone scan.
Immediately before being treated with ZIO-101, you will have another physical examination, you will also be asked about any medicines you are taking and how you are feeling. The blood tests may need to be repeated along with the EKG and the urine test. In addition, a small blood sample must be taken immediately before the injection of ZIO-101.
The injections of ZIO-101 will take approximately one hour. Following the first injection only, you will have 6 samples of blood taken at 0.5, 1, 2, 4, 8 and 12 hours. Additional blood samples will be taken prior to each dose of ZIO-101 only. You will also have repeat EKG within one hour after completing the injection. This process will be repeated for 5 consecutive days.
Your next visit will be Week 2 and at the onset of this visit, a blood sample will be taken and you will be asked how you feel. At Weeks 3 and 4, another blood sample will be taken and you will be asked how you feel.
At the end of Week 4, a new cycle begins. Immediately before being treated with ZIO-101, you will have a physical examination, you will be asked about any medicines you are taking and how you are feeling. The blood tests will be repeated along with the EKG and the urine test. In addition, any test used to measure your blood cancer will be repeated toward the end of the cycle.
You may receive up to six of these cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: ZIO-101 (Darinaparsin) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must have relapsed/refractory leukemia or lymphoma for which no standard therapies are anticipated to result in a durable remission. Relapsed/refractory leukemia/lymphoma includes acute leukemia, chronic myeloproliferative disease, chronic lymphoproliferative disease, multiple myeloma, and any type of lymphoma. Subjects with poor-risk myelodysplasia (MDS) are also candidates for this protocol. Poor risk MDS includes refractory anemia with excess blasts or excess blasts in transformation, and chronic myelomonocytic leukemia.
- ECOG performance status of ≤ 2.
- Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing subjects are excluded. Sexually active men must also use acceptable contraceptive methods. Pregnant and nursing subjects are excluded because the effects of ZIO-101 on a fetus or nursing child are unknown.
- Must be able and willing to give written informed consent.
- Absent rapidly progressing disease, the interval from cancer therapy should be ≥ 3 weeks. Subjects receiving hydroxyurea should be on stable dose ≥ 7 days before beginning treatment protocol. Persisting chronic toxicities from prior therapy must be ≤ grade 1.
Key exclusion criteria (7 listed)
- Subjects with any one of the following criteria will not be eligible for study participation:
- Patients with indolent and stable myeloma, MDS or CLL not requiring therapy are not eligible.
- Central nervous system (CNS) involvement with cancer.
- Uncontrolled active infection of any kind. Subjects with infections that are under active treatment with antibiotics and whose infections are controlled may be entered to the study.
- Active heart disease including myocardial infarction within previous 6 months; symptomatic coronary artery disease; any type of chronic, ongoing arrhythmias; or uncontrolled congestive heart failure.
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 |
|---|---|---|
| ZIO-101 (Darinaparsin)Also: ZIO-101ZIO-101 (Darinaparsin) given for five consecutive days to be repeated every 28 days for up to six months. This is a dose escalation study. | Drug | Single Arm |
Primary outcome
Response Rate
Time frame: 6 months
3 secondary outcomes
The RECIST criteria will be used for patients with all leukemias and myelodysplastic syndromes.
Time frame: 6 months
Patients with lymphoma or myeloma will be assessed by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas.
Time frame: 6 months
EBMT, IBMTR and ABMTR criteria for definition of response, relapse and progression in patients with multiple myeloma .
Time frame: 6 months
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 19 Jul 2012.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 ZIO-101 (Darinaparsin) in people with Acute Leukemia and Chronic Myeloproliferative Disease, run by Alaunos Therapeutics 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 10 inclusion and 7 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 19 Jul 2012. 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?
Response Rate (time frame: 6 months). 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 19 Jul 2012.