Leukemia
Conditions
Keywords
chronic myelogenous leukemia, BCR-ABL1 positive, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia
Brief summary
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with Philadelphia chromosome-positive chronic myelogenous leukemia.
Detailed description
OBJECTIVES: Primary * Determine the activity of bcr-abl p210-b3a2 breakpoint-derived pentapeptide vaccine (CMLVAX100), in terms of peripheral blood bcr-abl/abl ratio reduction, in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. Secondary * Determine the reduction of molecular residual disease at 3 months in patients treated with this vaccine. * Determine the reduction of molecular residual disease at 12 months in patients treated with maintenance boosts of this vaccine. * Determine the rate of complete molecular response at any time after vaccination. * Determine in vivo and in vitro peptide-specific immune response induced by the vaccine. OUTLINE: This is a prospective, nonrandomized, open-label, multicenter study. Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1 and 2 and bcr-abl p210-b3a2 breakpoint-derived pentapeptide vaccine (CMLVAX100) SC on day 2. Treatment repeats every 2 weeks for 6 courses. Patients then receive CMLVAX100 SC once monthly for 3 months and then once every 3 months for 6 months (for a total of 1 year). Patients may receive additional CMLVAX100 SC every 6 months for at least 3 years. Treatment continues in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 69 patients will be accrued for this study.
Interventions
BIOLOGICALbcr-abl p210-b3a2 breakpoint-derived multipeptide vaccine
BIOLOGICALsargramostim
Sponsors
Gruppo Italiano Malattie EMatologiche dell'Adulto
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of chronic myelogenous leukemia (CML) meeting the following criteria: * Philadelphia chromosome positive disease * b3a2 breakpoint mutation * Prior treatment with conventional imatinib mesylate for ≥ 18 months required * Complete cytogenetic response documented on ≥ 2 different examinations * Persistence of molecularly detectable residual disease (any level of bcr-abl transcript) * Patients continue to receive imatinib mesylate at the same dose (conventional treatment) during study treatment PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Bilirubin ≤ 2 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No severe active infection or other serious medical illness that would preclude study completion * No known immunodeficiency * No autoimmune disorders PRIOR CONCURRENT THERAPY: * No concurrent immunosuppression or systemic immunosuppressive medication * No concurrent dose escalation of imatinib mesylate * No other concurrent investigational products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Showing a Reduction by at Least 50% of Peripheral Blood BCR-ABL/ABL Ratio Compared to the Individual Prevaccine Level | At 6 and 9 months | Response rate evaluated after immunization and reinforcement boosts (evaluation after 6 months, ) and persisting at the 9th month (after 10th vaccination) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Undetectable Transcript at Any Time After Immunization | Up to 6 months | — |
| Number of Patients With Peptide-specific Immune Response Induced by the Vaccinations | At 9 months | A significant in vitro b3a2-peptide-specific CD4+ T cell proliferation |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chronic Myeloid Leukemia (CML) Patients Study population | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not evaluable for response | 14 |
Baseline characteristics
| Characteristic | Chronic Myeloid Leukemia (CML) Patients | — |
|---|---|---|
| Age, Continuous | 56.5 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Italy | 43 participants | — |
| Sex: Female, Male Female | 16 Participants | — |
| Sex: Female, Male Male | 27 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 43 |
| serious Total, serious adverse events | 0 / 43 |
Outcome results
Primary
Number of Patients Showing a Reduction by at Least 50% of Peripheral Blood BCR-ABL/ABL Ratio Compared to the Individual Prevaccine Level
Response rate evaluated after immunization and reinforcement boosts (evaluation after 6 months, ) and persisting at the 9th month (after 10th vaccination)
Time frame: At 6 and 9 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronic Myeloid Leukemia (CML) Patients | Number of Patients Showing a Reduction by at Least 50% of Peripheral Blood BCR-ABL/ABL Ratio Compared to the Individual Prevaccine Level | 50% reduction at 6 months | 22 participants |
| Chronic Myeloid Leukemia (CML) Patients | Number of Patients Showing a Reduction by at Least 50% of Peripheral Blood BCR-ABL/ABL Ratio Compared to the Individual Prevaccine Level | 50% reduction at 9 months | 14 participants |
Secondary
Number of Patients With Peptide-specific Immune Response Induced by the Vaccinations
A significant in vitro b3a2-peptide-specific CD4+ T cell proliferation
Time frame: At 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronic Myeloid Leukemia (CML) Patients | Number of Patients With Peptide-specific Immune Response Induced by the Vaccinations | 29 participants |
Secondary
Number of Patients With Undetectable Transcript at Any Time After Immunization
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chronic Myeloid Leukemia (CML) Patients | Number of Patients With Undetectable Transcript at Any Time After Immunization | 14 participants |