Bortezomib in Treating Patients With Advanced Myeloproliferative Disorders

NCT00437086 | Completed Early Phase 1 DMC

• 5 other identifiers: CDR0000529906P30CA015083MC0486695-05VEL-04-107
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Bortezomib may stop the growth of abnormal cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the abnormal cells. PURPOSE: This clinical trial is studying the side effects and how well bortezomib works in treating patients with advanced myeloproliferative disorders.

Conditions

Chronic Myeloproliferative Disorders; Leukemia

Keywords

chronic myelomonocytic leukemia; primary myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Number and severity of toxicities as assessed by NCI CTCAE v3.0

  40 weeks

• Proportion of patients who show treatment success, as defined by anemia, spleen, bone marrow, or constitutional symptoms' response (complete, partial, major, or minor response)

  40 weeks

Secondary Outcomes (1)

• Effects of treatment, in terms of changes in bone marrow cellularity, tryptase-positive mast cells, reticulin fibrosis, osteosclerosis, and angiogenesis, in responding patients

  40 weeks

Study Arms (1)

PS-341

EXPERIMENTAL

Designed to assess the toxicity and pilot response of PS-341 in patients with advanced myeloproliferative diseases.

Drug: PS-341

Interventions

PS-341 DRUG

1.6 mg/m2 by IV; 4 out of 5 weeks

Also known as: Bortezomib, Velcade, MLN-341, LDP-341

PS-341

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed advanced myeloproliferative disorder, including 1 of the following subtypes: * Myelofibrosis with myeloid metaplasia defined by the following criteria: * Evaluable or symptomatic disease as evidenced by ≥ 1 of the following: * Anemia, defined as hemoglobin \< 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks * Symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment\* NOTE: \*Subjective but painful enough to mandate intervention * Chronic myelomonocytic leukemia (CMML) defined by the following criteria: * Absence of an imatinib mesylate-sensitive molecular abnormality for CMML (i.e., t\[5;12\], t\[5;10\], t\[1;5\], and t\[5;7\]) confirmed by fluorescent in situ hybridization (FISH) or standard cytogenetic bone marrow analysis within the past 18 months * Symptomatic disease as evidenced by ≥ 1 of the following: * Anemia, defined as hemoglobin \< 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks * Palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment\* NOTE: \*Subjective but painful enough to mandate intervention * Leukocytosis associated with ascites, serositis, pleural effusions, vasculitis, or other overt manifestation * Systemic mast cell disease defined by the following criteria: * Absence of the FIP1LI-PDGFRA mutation as confirmed by FISH * Evaluable and symptomatic disease requiring therapy, as evidenced by involvement with organs other than skin (i.e., heart, bowel, peripheral blood, liver/spleen, or marrow) * Debilitating mast cell mediator symptoms not responsive to standard therapy such as antihistamines * Absence of t(9;22) translocation as confirmed by FISH or standard cytogenetic peripheral blood or marrow analysis at any prior time point PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Not incarcerated in a municipal, county, state, or federal prison * Absolute neutrophil count ≥ 1,000/mm³ * Platelet count ≥ 75,000/mm³ * Creatinine ≤ 2.0 mg/dL * Total or direct bilirubin ≤ 2.0 mg/dL * AST and ALT ≤ 3 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis) * No baseline peripheral or autonomic neuropathy ≥ grade 2 * No other condition or laboratory abnormality that would place the patient at unacceptable risk or confound the ability to interpret study data * No hypersensitivity to boron, mannitol, or bortezomib * No myocardial infarction within the past 6 months * No New York Hospital Association class III-IV heart failure * No uncontrolled angina * No severe uncontrolled ventricular arrhythmia * No evidence of acute ischemia or active conduction system abnormality by ECG * ECG screening abnormalities must be documented as not medically relevant * No other serious medical or psychiatric illness that would preclude study participation PRIOR CONCURRENT THERAPY: * At least 14 days since prior chemotherapy (e.g., interferon alfa, anagrelide, or other myelosuppressive agent) or any other experimental therapy * At least 14 days since prior growth factors * At least 14 days since prior systemic use of corticosteroids * More than 14 days since prior investigational drugs * Concurrent hydroxyurea allowed for ≤ 14 days during study therapy if clinically indicated for extreme leukocytosis control

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Leukemia, Myelomonocytic, Chronic; Primary Myelofibrosis

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ruben A. Mesa, M.D.

  Mayo Clinic

  STUDY CHAIR

• Candido E. Rivera, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2007
• First Posted: February 19, 2007
• Study Start: September 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: October 17, 2014

Record last verified: 2014-10

Locations

US (3)