Clinical trial NCT01073436: Discontinuation of Imatinib Mesylate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With Interferon-Alpha
Official title: Discontinuation of Tyrosine Kinase Inhibitor Therapy in Patients With Chronic-Phase Chronic Myeloid Leukemia, Previously Treated With Interferon-Alpha
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Chronic Myeloid Leukemia
Keywords: diagnosis of Ph+) CML in chronic phase.
prior therapy with interferon-alpha for at least 2 years, and achieved at least a partial cytogenetic response
receiving a TKI (imatinib mesylate, dasatinib, nilotinib)
WBC ≤ 10 x 109/L.
Platelet count < 450,000 x 109/L.
No blasts or promyelocytes in peripheral blood.
No evidence of disease-related symptoms and extramedullary disease
complete cytogenetic response (CCyR) on a TKI for a minimum of 1 yr
major molecular remission on a TKI for a minimum of 1 yr
18 years of age or older
ECOG performance status of 0-2 (Appendix 13.1)
Informed Consent
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2010-02-23
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Diagnosed with Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase.

Brief summary: To investigate whether patients with chronic-phase chronic myeloid leukemia (CP-CML) previously treated with interferon-alpha (IFN) and presently on a tyrosine kinase inhibitor (TKI) (imatinib mesylate, dasatinib, or nilotinib) with achievement of a complete cytogenetic and at least a major molecular remission, are able to discontinue therapy and maintain a durable remission. Relapse-free survival (RFS) rate at 1 year after discontinuation of TKI will be the measurement of this objective.


Eligibility criteria: Inclusion Criteria:

1. Patients must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic myeloid leukemia in chronic phase.
2. Patients must have received prior therapy with interferon-alpha for their CML, for a period of at least 2 years, and achieved at least a partial cytogenetic response on this therapy, defined as 1% - 34% Ph+ cells in metaphase, present in the bone marrow.
3. Patients must be actively receiving treatment for their CML with a TKI (imatinib mesylate, dasatinib, nilotinib). If patients are receiving dasatinib or nilotinib, this can only be for reasons other than imatinib-resistant CML.
4. Patients must have an ongoing complete hematologic response (CHR) on a TKI, defined as follows:

   * WBC ≤ 10 x 109/L.
   * Platelet count \< 450,000 x 109/L.
   * No blasts or promyelocytes in peripheral blood.
   * No evidence of disease-related symptoms and extramedullary disease, including the liver and spleen.
5. Patients must have a complete cytogenetic response (CCyR) on a TKI for a minimum of one year leading up to enrollment. Complete cytogenetic response is defined as 0% Ph+ cells in metaphase, in the bone marrow and/or a negative peripheral blood FISH analysis for the BCR/ABL gene fusion, and an ongoing CCyR must be confirmed by bone marrow aspirate cytogenetics and/or peripheral blood FISH for BCR/ABL within 4 weeks of discontinuing therapy.
6. Patients must have at least a major molecular remission on a TKI for a minimum of 1 year, present on 2 consecutive analyses, performed at least 3 months apart, in the 6 to 12 months leading up to enrollment. Major molecular remission is defined as ≥ 3 log reduction from a standard baseline value (equivalent to a BCR-ABL/ABL of ≤ 0.1%) in BCR/ABL transcript by quantitative RT-PCR performed on peripheral blood or bone marrow aspirate. Complete molecular remission is defined as a negative quantitative RT-PCR (QPCR) analysis for BCR/ABL, present on 2 consecutive analyses, performed at least 3 months apart, in the 6 to 12 months leading up to enrollment.
7. Patients must be eighteen years of age or older
8. Patients must have an ECOG performance status of 0-2 (Appendix 13.1)
9. All patients must be informed of the investigational nature of this study and standard alternative therapy. All patients must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

1. Patients who have had prior progression of their CML to accelerated phase or blast crisis.
2. Patients who have previously undergone hematopoietic stem cell transplantation.
3. Patients receiving dasatinib or nilotinib due to a prior history of imatinib-resistant CML.
4. Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable.

Primary outcomes:
measure: Relapse-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Reduction of the malignant stem cell population
timeFrame: 1 Year
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Dale Bixby, M.D./PhD
role: PRINCIPAL_INVESTIGATOR
References: