Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI

OBJECTIVES:

Primary

- Compare clinical response, in terms of 1-year progression-free survival and rate of
molecular complete remission, in patients with Philadelphia chromosome-positive chronic
myelogenous leukemia (Ph+ CML) in chronic phase who have achieved a complete cytogenetic
remission to single-agent tyrosine kinase inhibitor treated with interferon alfa and
sargramostim (GM-CSF) vs tyrosine kinase inhibitor and GM-K562 cell vaccine.

Secondary

- Compare time to Ph-negativity by polymerase chain reaction after randomization.

- Compare disease-free survival and percent molecular complete remissions.

- Determine the toxicity of these treatment regimens in these patients.

OUTLINE: This is a multicenter, randomized, crossover, study. Patients are randomized to 1 of
2 treatment arms. The study will be modified based on the results of the planned interim
analysis. Individual Study Arms will continue to accrue and treat as indicated by the
analysis. The study in its current format will continue should the planned interim analysis
indicate both Study Arms remain viable as effective treatments.

All patients continue to receive their standard dose of tyrosine kinase inhibitor in addition
to 1 of the following treatment arms:

- Arm I : Patients receive interferon alfa subcutaneously (SC) and GM-CSF SC once daily
for 6 months. Patients who achieve a molecular complete remission (CR) (defined as
BCR-ABL-negative disease confirmed by 2 PCR assays separated by 1 month) at the end of
the 6-month period, discontinue study therapy and are monitored for disease recurrence
by blood tests every 4 weeks. Patients who do not achieve a molecular CR (defined as
BCR-ABL-positive disease) after completion of the initial 6 months of therapy, receive
an additional 6 months of therapy as above. Patients who achieve BCR-ABL-negative
disease during the additional 6 months of therapy, discontinue study therapy and are
monitored for disease recurrence by blood tests every 4 weeks. Patients who remain
BCR-ABL-positive by PCR after an additional 6 months of therapy, are eligible to cross
over to arm II.

If at any time after stopping study therapy blood tests show disease recurrence, patients
restart tyrosine kinase inhibitor and are eligible to cross over to arm II. Patients are also
eligible to cross over to arm II in the presence of unacceptable toxicity.

- Arm II: Patients receive GM-K562 cell vaccine intradermally once every 3 weeks for a
minimum of 6 months. Patients with BCR-ABL-negative disease at the end of the 6-month
period discontinue study therapy and are monitored for disease recurrence by blood tests
every 4 weeks. Patients with BCR-ABL-positive disease after the completion of the
initial 6 months of therapy, receive an additional 6 months of therapy as above.
Patients who achieve BCR-ABL-negative disease during the additional 6 months of therapy,
discontinue study therapy and are monitored every 4 weeks for disease recurrence.
Patients who remain BCR-ABL-positive after the additional 6 months of therapy, are
eligible to cross over to arm I.

If at any time after stopping study therapy blood tests show disease recurrence, patients
restart tyrosine kinase inhibitor and are eligible to cross over to arm I. Patients are also
eligible to cross over to arm I in the presence of unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 1 year.

As of May 2014, Study Arm B is not available to newly accrued and enrolled subjects based on
the interim analysis directing all new subjects to the combination of Interferon + GM-CSF.

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Diagnosis of chronic myelogenous leukemia (CML) in chronic phase based on cytogenetic
detection of the Philadelphia chromosome and/or detection of the BCR-ABL rearrangement
by any of the following molecular methods:

- Recombinant DNA analysis of the BCR-ABL fusion gene

- Fluorescence in situ hybridization (FISH)

- Polymerase chain reaction detection of the BCR-ABL hybrid mRNA

- Documentation of complete cytogenetic response by conventional cytogenetic or FISH
analysis while on a stable dose of tyrosine kinase inhibitor

- No other phase of CML

PATIENT CHARACTERISTICS:

- ECG performance status 0-2

- Life expectancy > 24 months

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- Creatinine ≤ 2.0 mg/dL

- Bilirubin ≤ 2.0 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- No other malignancy within the past 5 years except in situ cervical carcinoma or
adequately treated nonmelanoma skin cancer

- No other disease requiring long-term corticosteroids or immunosuppressants

PRIOR CONCURRENT THERAPY:

- At least 28 days since prior investigational agents

- No prior bone marrow transplant or other transplant

- No concurrent immunosuppressants (e.g., steroids, cyclosporine, azathioprine,
mycophenolate mofetil, sirolimus, or tacrolimus)

- No concurrent hydroxyurea, busulfan, or cytoreductive agents (other than frontline
TKI)

- No other concurrent anticancer agents or therapies