Clinical trial NCT00466726: Vaccine Therapy in Treating Patients With Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia
Official title: Phase II Multicenter Study of P210-B3A2 Derived Peptide Vaccine in Chronic Myeloid Leukemia Patients in Complete Cytogenetic Response With Persistent Molecular Residual Disease During Imatinib Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
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
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2007-04-27
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of Patients Showing a Reduction by at Least 50% of Peripheral Blood BCR-ABL/ABL Ratio Compared to the Individual Prevaccine Level
timeFrame: At 6 and 9 months
Secondary outcomes:
measure: Number of Patients With Undetectable Transcript at Any Time After Immunization
timeFrame: Up to 6 months
measure: Number of Patients With Peptide-specific Immune Response Induced by the Vaccinations
timeFrame: At 9 months
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Bergamo
country: Italy
facility: Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: Istituto di Ematologia "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi
city: Brescia
country: Italy
facility: USD Trapianti di midollo per adulti - Cattedra di Ematologia - Università degli Studi di Brescia
city: Catania
country: Italy
facility: Università di Catania - Cattedra di Ematologia - Ospedale 'Ferrarotto'
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Naples
country: Italy
facility: Federico II University Medical School
city: Novara
country: Italy
facility: S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
city: Orbassano
country: Italy
facility: Azienda Ospedale S. Luigi at University of Torino
city: Palermo
country: Italy
facility: spedali Riuniti "Villa Sofia-Cervello"
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Universita Degli Studi "La Sapeinza"
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Rossano
country: Italy
facility: Unità Operativa di Oncologia - Presidio Ospedaliero N. Giannetasio - Azienda ASL 3
city: Sassari
country: Italy
facility: Ematologia - Dipartimento di Medicina Clinica e Sperimentale
city: Siena
country: Italy
facility: Nouvo Policlinico "LE SCOTTE'
city: Udine
country: Italy
facility: Policlinico Universitario Udine
Study officials:
affiliation: Nouvo Policlinico "LE SCOTTE'
name: Monica Bocchia, MD
role: STUDY_CHAIR
References:
citation: BCR-ABL Derived Peptide Vaccine in Chronic Myeloid Leukemia Patients with Molecular Minimal Residual Disease During Imatinib: Interim Analysis of a Phase 2 Multicenter GIMEMA CML Working Party Trial.