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
18 Years
65 Years
Both
Chronic Myeloid Leukemia
Trial Information
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
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.
Inclusion Criteria:
1. Age 18-65 years
2. First chronic phase
3. Performance status (ECOG/WHO) < or = 2
4. Written informed consent
Exclusion Criteria:
1. Age <18 or >65 years
2. Second chronic, accelerated or blastic phase
3. Performance status (ECOG/WHO) > 2
4. Inability to provide written informed consent
5. Prior treatment with STI 571 or alfaIFN
6. Prior alloBMT
7. Prior autoBMT
8. Prior non-conventional, intensive chemotherapy in the last 12 months
9. Prior experimental agents in the last 60 days
10. 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)
11. Pregnancy
12. Formal refusal of any recommendation of a safe contraception
13. Alcohol or drug addiction
14. Positivity for HBV, HCV or HIV
15. Altered hepatic or renal function as defined by AST/ALT or bilirubine > 3 times upper
normal limits (UNL) and by creatinine > or = 20mg/L
16. 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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Principal Investigator
Michele Baccarani, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Istituto di Ematologia "L e A Seragnoli" Bologna
Authority:
Italy: Ethics Committee
Study ID:
CML 011
NCT ID:
NCT00511121
Start Date:
April 2001
Completion Date:
Related Keywords:
- Chronic Myeloid Leukemia
- chronic myeloid leukemia
- tyrosine kinase
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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