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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00363649
First received: August 10, 2006
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: GM-K562 cell vaccine
Biological: recombinant interferon alfa
Biological: sargramostim
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Interferon + GM-CSF Versus K562/GM-CSF Vaccination in CML Patients Achieving a Complete Cytogenetic Response to Frontline Tyrosine Kinase Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression-free survival at 1 year [ Designated as safety issue: No ]
  • Rate of molecular complete remission [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Philadelphia chromosome (Ph) negativity as measured by polymerase chain reaction [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Percent molecular complete remission [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Time to progression [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: September 2006
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients will receive injections of interferon alfa and GM-CSF once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II.
Biological: recombinant interferon alfa
Given by injection
Biological: sargramostim
Given by injection
Experimental: Arm II
Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I.
Biological: GM-K562 cell vaccine
Given by injection

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.

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.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00363649

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: B. Douglas Smith, MD    410-614-5068    bdsmith@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: B. Douglas Smith, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00363649     History of Changes
Other Study ID Numbers: J05121 CDR0000492005, P30CA006973, JHOC-J05121
Study First Received: August 10, 2006
Last Updated: December 10, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Philadelphia chromosome positive chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Interferon-alpha
Interferon Alfa-2a
Interferons
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 10, 2014