Chronic Myeloid LeukemiaPhase 2NCT00511121
Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON)
A Phase 2 study testing STI571 and PEG INTRON in people with Chronic Myeloid Leukemia, run by University of Bologna.
Trial summary
This is a phase II multicenter, open-label study designed to investigate the feasibility (tolerance, compliance and safety) of a combination of the tyrosine kinase inhibitor STI 571 (GLIVEC, Novartis Pharma) with a pegylated *-Interferon 2b (PEG INTRON). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- STI571 and PEG INTRON
- How many people
- 5 participants
- Where
- No sites listed yet
- Study dates
- Apr 2001to not given
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65 years
- First chronic phase
- Performance status (ECOG/WHO) < or = 2
- Written informed consent
Who cannot join
- Age <18 or >65 years
- Second chronic, accelerated or blastic phase
- Performance status (ECOG/WHO) > 2
- Inability to provide written informed consent
- Prior treatment with STI 571 or alfaIFN
- Prior alloBMT
Show all 16Show fewer
- Prior autoBMT
- Prior non-conventional, intensive chemotherapy in the last 12 months
- Prior experimental agents in the last 60 days
- Prior conventional chemotherapy in the last 60 days (in case of Busulfan or other alkylating agents) or in the last 10 days (in case of Hydroxyurea or other cell-cycle dependent drugs)
- Pregnancy
- Formal refusal of any recommendation of a safe contraception
- Alcohol or drug addiction
- Positivity for HBV, HCV or HIV
- Altered hepatic or renal function as defined by AST/ALT or bilirubine > 3 times upper normal limits (UNL) and by creatinine > or = 20mg/L
- Any other disease or condition that by the advise of the responsible physician would make the treatment dangerous for the patient or would make the patient ineligible for the study, including physical, psychiatric, social and behavioural problems.
About this study
Official title: An Exploratory Phase II Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON) in the Treatment of Chronic Myeloid Leukemia in Chronic Phase
This is a phase II multicenter, open-label study designed to investigate the feasibility (tolerance, compliance and safety) of a combination of the tyrosine kinase inhibitor STI 571 (GLIVEC, Novartis Pharma) with a pegylated *-Interferon 2b (PEG INTRON). The rationale for testing this combination is that 1) aIFN is curently the first line agent for the treatment of CML, 2) the pegylated formulation of aIFN is more convenient and is better tolerated than the conventional formulation, 3) STI571 is currently the most promising investigational agent for the treatment of CML because it is targeted to the molecular bases of the disease, is effective also in the advanced phases of the disease, and is effective also in the cases who are resistant to aIFN, 4) the mechanisms of action of the two agents are different. Therefore the combination of STI571 and PEGINTRON is likely to provide the best treatment of CML and to be tested very soon in randomized phase III studies of efficacy. So far STI571 and PEGINTRON have been investigated separately. The present study is an exploratory study that has been planned with the aim of evaluating the adverse events and the safety of the combination, so as to identify a safe and tolerable regime that can be tested prospectively for efficacy in a subsequent, randomized phase III study. Based on available knowledge and data, STI571 is more specific and can be more effective than PEGINTRON. Therefore in this exploratory study STI571 is given a priority over PEGINTRON as to dose and dose adaptation. Sixty subjects with chronic phase CML, previously untreated with any one of study drugs, will be enrolled over a 3 months period and will be treated and studied for 12 months. The patients can be pretreated with hydroxyurea , whenever required, hence are treated with STI 571 at a fixed dose (400mg) and with PEG-Intron at doses ranging from 50 to 150 *g weekly (the first cohort of 20 patients at 50 *g/w, the second cohort of 20 patients at 100 *g/w and the third cohort of 20 patients at 150 *g/w). The response (hematologic, cytogenetic and molecular) to the combination treatment will be evaluated every 3 months, and the pharmacokinetics of study drugs will be studied in a sample of study patients. The duration of the study is 12 months, for a total trial time of 15 months.
Read the detailed description
STI 571 and *IFN are the two single most effective agents for the treatment of CML. Their mechanisms of actions are different. Their toxicity is also different, but both spare normal hemopoietic stem cells. STI 571 is well tolerated, while conventional *IFN is poorly tolerated, especially in the elderly. PEG *IFNs are going to substitute for conventional *IFNs because of a better pharmacokinetic and toxicity profile and because require less injections (once a week vs. once a day).Resistance to IFN (6-13) and to STI571 (29-34) occurs in vitro and in vivo, where it increases with time for IFN and is also expected to increase with time for STI571. STI571 and IFN have different mechanisms of action and it has been shown in vitro that the combination of STI571 with alfaIFN is more toxic than either agent alone against Ph positive cells (35-37). Therefore, a combination of STI 571 with a PEG *IFN is worth testing. A phase II, dose-finding, exploratory study is required to investigate feasibility, toxicity, safety and tolerability of the combination. In CML, PEG INTRON studies are more advanced than PEGASIS studies. These considerations provide the rationale for this phase II study of STI 571 and PEG INTRON in CML.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- STI571 and PEG INTRON
- Keywords
- chronic myeloid leukemia, tyrosine kinase
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STI571 and PEG INTRONDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
This is a study that is designed to determine the AE and the safety of a combination of standard dose of STI 571 (400 my daily) with a low-intermediate dose of *IFN (50 t0 150 ug weekly) and the compliane of the patients to the combination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2007 (estimated)
- Study startApr 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants
Sponsor and investigators
- Lead sponsor
- University of Bologna
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Schering-Plough
- Investigators
- Michele Baccarani, MD, Principal investigator, Istituto di Ematologia "L e A Seragnoli" Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00511121
- Sponsor's protocol ID
- CML 011
- Status last verified
- Aug 2007
- First submitted
- 2 Aug 2007
- Last updated
- 3 Aug 2007
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Phase II Study of the Combination of a Tyrosine Kinase Inhibitor (STI571) and a Pegylated Human Recombinant Interferon alfa2b (PEGINTRON) in the Treatment of Chronic Myeloid Leukemia in Chronic Phase
- ClinicalTrials.gov ID
- NCT00511121
- Acronym / sponsor ID
- CML 011
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- chronic myeloid leukemia, tyrosine kinase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants
- Lead sponsor
- University of BolognaUniversity, hospital or other
- Collaborators
- Novartis, Schering-Plough
- Study start
- Apr 2001
- First posted
- 3 Aug 2007 (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 is a phase II multicenter, open-label study designed to investigate the feasibility (tolerance, compliance and safety) of a combination of the tyrosine kinase inhibitor STI 571 (GLIVEC, Novartis Pharma) with a pegylated *-Interferon 2b (PEG INTRON). The rationale for testing this combination is that 1) aIFN is curently the first line agent for the treatment of CML, 2) the pegylated formulation of aIFN is more convenient and is better tolerated than the conventional formulation, 3) STI571 is currently the most promising investigational agent for the treatment of CML because it is targeted to the molecular bases of the disease, is effective also in the advanced phases of the disease, and is effective also in the cases who are resistant to aIFN, 4) the mechanisms of action of the two agents are different. Therefore the combination of STI571 and PEGINTRON is likely to provide the best treatment of CML and to be tested very soon in randomized phase III studies of efficacy. So far STI571 and PEGINTRON have been investigated separately. The present study is an exploratory study that has been planned with the aim of evaluating the adverse events and the safety of the combination, so as to identify a safe and tolerable regime that can be tested prospectively for efficacy in a subsequent, randomized phase III study. Based on available knowledge and data, STI571 is more specific and can be more effective than PEGINTRON. Therefore in this exploratory study STI571 is given a priority over PEGINTRON as to dose and dose adaptation. Sixty subjects with chronic phase CML, previously untreated with any one of study drugs, will be enrolled over a 3 months period and will be treated and studied for 12 months. The patients can be pretreated with hydroxyurea , whenever required, hence are treated with STI 571 at a fixed dose (400mg) and with PEG-Intron at doses ranging from 50 to 150 *g weekly (the first cohort of 20 patients at 50 *g/w, the second cohort of 20 patients at 100 *g/w and the third cohort of 20 patients at 150 *g/w). The response (hematologic, cytogenetic and molecular) to the combination treatment will be evaluated every 3 months, and the pharmacokinetics of study drugs will be studied in a sample of study patients. The duration of the study is 12 months, for a total trial time of 15 months.
Detailed description
STI 571 and *IFN are the two single most effective agents for the treatment of CML. Their mechanisms of actions are different. Their toxicity is also different, but both spare normal hemopoietic stem cells. STI 571 is well tolerated, while conventional *IFN is poorly tolerated, especially in the elderly. PEG *IFNs are going to substitute for conventional *IFNs because of a better pharmacokinetic and toxicity profile and because require less injections (once a week vs. once a day).Resistance to IFN (6-13) and to STI571 (29-34) occurs in vitro and in vivo, where it increases with time for IFN and is also expected to increase with time for STI571. STI571 and IFN have different mechanisms of action and it has been shown in vitro that the combination of STI571 with alfaIFN is more toxic than either agent alone against Ph positive cells (35-37). Therefore, a combination of STI 571 with a PEG *IFN is worth testing. A phase II, dose-finding, exploratory study is required to investigate feasibility, toxicity, safety and tolerability of the combination. In CML, PEG INTRON studies are more advanced than PEGASIS studies. These considerations provide the rationale for this phase II study of STI 571 and PEG INTRON in CML.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-65 years
- First chronic phase
- Performance status (ECOG/WHO) < or = 2
- Written informed consent
Key exclusion criteria (16 listed)
- Age <18 or >65 years
- Second chronic, accelerated or blastic phase
- Performance status (ECOG/WHO) > 2
- Inability to provide written informed consent
- Prior treatment with STI 571 or alfaIFN
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 |
|---|---|---|
| STI571 and PEG INTRON | Drug | – |
Primary outcome
This is a study that is designed to determine the AE and the safety of a combination of standard dose of STI 571 (400 my daily) with a low-intermediate dose of *IFN (50 t0 150 ug weekly) and the compliane of the patients to the combination.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2007.
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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.
Michele Baccarani, MD principal investigator
Istituto di Ematologia "L e A Seragnoli" Bologna
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing STI571 and PEG INTRON in people with Chronic Myeloid Leukemia, run by University of Bologna.
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 4 inclusion and 16 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: stopped early, as of the sponsor's last update on 3 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early. Results are not available in the source record.
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?
This is a study that is designed to determine the AE and the safety of a combination of standard dose of STI 571 (400 my daily) with a low-intermediate dose of *IFN (50 t0 150 ug weekly) and the compliane of the patients to the combination.. 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 3 Aug 2007.