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

NCT ID: NCT00363649

Last Updated: 2018-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2017-09-30

Brief 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.

Conditions

Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Patients will receive injections of interferon alfa and sargramostim 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.

Group Type: EXPERIMENTAL

Interferon alfa

Intervention Type: BIOLOGICAL

Given by injection

Sargramostim

Intervention Type: BIOLOGICAL

Given by injection

Arm B

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. NOTE: 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 + sargramostim (Arm A).

Group Type: EXPERIMENTAL

GM-K562 cell vaccine

Intervention Type: BIOLOGICAL

Given by injection

Interventions

GM-K562 cell vaccine

Given by injection

Intervention Type: BIOLOGICAL

Interferon alfa

Given by injection

Intervention Type: BIOLOGICAL

Sargramostim

Given by injection

Intervention Type: BIOLOGICAL

Other Intervention Names

GM-CSF

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

B. Douglas Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J05121

Identifier Type: -

Identifier Source: org_study_id