Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Tyrosine kinase inhibitors may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Interferon alfa may interfere with the growth of cancer
      cells. GM-CSF may help cells that are involved in the body's immune response work better.
      Vaccines made from a person's cancer cells may help the body build an effective immune
      response to kill cancer cells.

      PURPOSE: This randomized phase II trial is studying tyrosine kinase inhibitors, interferon
      alfa, and GM-CSF to see how well they work compared to tyrosine kinase inhibitors and vaccine
      therapy in treating patients with chronic phase chronic myelogenous leukemia.
    

Detailed description: 
      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.
    

Intervention name(s): GM-K562 cell vaccine; Interferon alfa; Sargramostim
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Given by injection; Given by injection; Given by injection
Other intervention name(s): GM-CSF
Intervention MeSH terms: Interferons; Interferon-alpha; Sargramostim
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants were randomly assigned to Arm A or Arm B and received up to twelve months of protocol therapy. If at any point a participant progressed, relapsed, or had unacceptable toxicity, they could cross over to the other arm. Participants could only cross over once.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Philadelphia chromosome positive chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia