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A Combination of Imatinib or Nilotinib Together With Pegylated Interferon-α2b in Chronic-Phase Chronic Myeloid Leukemia: A Phase II Pilot Study Targeting Both the Primitive and Differentiated CML Progenitor Populations


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Chronic Myeloid Leukemia

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Trial Information

A Combination of Imatinib or Nilotinib Together With Pegylated Interferon-α2b in Chronic-Phase Chronic Myeloid Leukemia: A Phase II Pilot Study Targeting Both the Primitive and Differentiated CML Progenitor Populations


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.

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Relapse-free survival (RFS) rate 1 year after discontinuation of the TKI and IFN

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Dale L. Bixby, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan

Authority:

United States: Food and Drug Administration

Study ID:

UMCC 2006.128

NCT ID:

NCT00573378

Start Date:

October 2007

Completion Date:

June 2015

Related Keywords:

  • Chronic Myeloid Leukemia
  • CML
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase

Name

Location

Universtiy of MichiganAnn Arbor, Michigan  48109