Imatinib or Nilotinib With Pegylated Interferon-α2b in Chronic Myeloid Leukemia
Condition: Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intervention: PEG-IFN-a2b
Intervention description: Patients will receive pegylated interferon α-2b (Pegintron®) (PEG-IFN-α2b) 150 µg subcutaneously, once a week. Patients and/or caregivers identified by the patient will be taught how to perform subcutaneous injections of the PEG-IFN-α2b by trained nurses in the chemotherapy infusion center at the University of Michigan Comprehensive Cancer Center. Those patients who do not feel comfortable receiving the injections outside of the cancer center, or are deemed unreliable in administering injections per the training nurse, will return to the cancer center infusion room on a weekly basis to receive subsequent injections.
Intervention MeSH terms: Peginterferon alfa-2b
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CML

Summary:

      To investigate whether patients with chronic-phase chronic myeloid leukemia (CP-CML) who have
      achieved a complete cytogenetic response (CCyR) on imatinib (IM) or nilotinib (N) can then be
      treated with a combination of the tyrosine kinase inhibitor (TKI) and interferon-α2b
      (PEG-IFN-a2b, [IFN]) for 2 years, subsequently have their therapy discontinued, and then
      maintain a durable molecular response off all therapy. Relapse-free survival (RFS) rate 1
      year after discontinuation of the TKI and IFN will be the measurement of this objective.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of Philadelphia chromosome positive (Ph+) chronic
             myeloid leukemia in chronic phase by having met all of the following criteria at the
             time of their initial diagnosis:

          -  Cytogenetic confirmation of Philadelphia chromosome or variants of the t(9;22)
             translocations. Patients may have secondary chromosomal abnormalities in addition to
             the Philadelphia chromosome.

          -  Peripheral blood or bone marrow blast count < 10%.

          -  Peripheral blood basophil count < 20%.

          -  Platelet count ≥ 100,000 x 109/L.

          -  If the peripheral blood counts are unavailable from the time of their original
             diagnosis, but there is no evidence of accelerated- or blast-phase disease from prior
             clinical or other medical records, then they will be allowed to participate.

          -  Patients must be eighteen years of age or older.

          -  Patients must be actively receiving treatment for their CML with a a tyrosine kinase
             inhibitor, either imatinib or nilotinib.

          -  Patients may be receiving imatinib mesylate. Patients must be on imatinib mesylate for
             a minimum of 2 years, and be on a stable dose for at least one consecutive year
             leading up to enrollment.

          -  Patients may be receiving nilotinib (Tasigna) as frontline therapy or as second line
             therapy if the reason for the switch from imatinib to nilotinib was intolerance to
             imatinib. Patients cannot have been switched from imatinib to nilotinib because of a
             concern or demonstration for resistance to frontline imatinib. Patients must be on
             nilotinib for a minimum of 2 years, and be on a stable does for at least one
             consecutive year leading up to enrollment.

          -  Patients must have an ongoing complete hematologic response (CHR) on a a TKI (imatinib
             or nilotinib), 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.

          -  Patients must have a complete cytogenetic response (CCyR) on a TKI (imatinib or
             nilotinib) for a minimum of 1 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 starting treatment.

          -  Patients may have a negative quantitative RT-PCR (qPCR) for BCR-ABL at the time of
             enrollment, but if the qPCR is positive, patients cannot have greater than 1% bcr-ABl
             / Abl /ABL transcript, present in 2 consecutive qPCR analyses, performed at least 3
             months apart, in the 6 to 12 months leading up to enrollment.

          -  Patients must have an ECOG performance status of 0-2 (Appendix 13.1).

          -  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:

          -  Patients who have had prior progression of their CML to accelerated phase or blast
             crisis.

          -  Patients who have previously undergone hematopoietic stem cell transplantation.

          -  Patients who have previously been treated with interferon-α.

          -  Patients with an absolute neutrophil count (ANC) < 1500/mm3 and/or a platelet count <
             100,000/mm3.

          -  Patients with serum bilirubin, SGOT[AST], SGPT[ALT], or serum creatinine > 1.5 x the
             upper limit of normal (ULN).

          -  Patients with an INR or PTT > 1.5 x ULN, with the exception of patients on treatment
             with oral anticoagulants.

          -  Patients with uncontrolled medical diseases such as diabetes mellitus,
             neuropsychiatric disorders, infection, angina, severe hypertension, pulmonary disease
             (chronic obstructive pulmonary disease [COPD] with hypoxemia), major organ malfunction
             (liver, kidney) or class III or IV cardiac disease as defined by the New York Heart
             Association Criteria.

          -  Patients who are (a) pregnant, (b) breast feeding, (c) of childbearing potential
             without a negative pregnancy test prior to Study Day 1, and (d) male or female of
             childbearing potential unwilling to use barrier contraceptive precautions throughout
             the trial (postmenopausal women must be amenorrheic for at least 12 months to be
             considered of non-childbearing potential).

          -  Patients with a history of another active malignancy within the last five years, which
             required treatment with chemotherapy, hormonal therapy, or radiation therapy.
             Exceptions to this rule include basal cell and squamous cell skin carcinomas or
             cervical carcinoma in situ.

          -  Patients with a history of non-compliance to medical regimens or who are considered
             potentially unreliable.