Filgrastim in Treating Patients With Bortezomib-, Carfilzomib-, or IMID-Refractory Multiple Myeloma

NCT01537861 | Terminated Early Phase 1

• 1 other identifier: 201204086
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Based on the pre-clinical data the investigators hypothesize that G-CSF treatment in patients with multiple myeloma will generate a 'hostile' bone marrow microenvironment for myeloma cells, depriving them of key support signals and rendering them more sensitive to chemotherapy. The investigators therefore propose to do an initial pilot study 1) to explore the safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with bortezomib-, carfilzomib-, or IMID-refractory myeloma and 2) to generate correlative data for a subsequent larger study looking at the combination.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Safety of the combination of G-CSF and bortezomib-, carfilzomib-, or IMID-based treatment regimens in patients with refractory multiple myeloma.

  Number and grade of adverse events based on NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  Up to 30 days after last treatment

Secondary Outcomes (5)

• Effects of G-CSF on bone marrow and bone marrow cytokine and chemokine levels. Including: Quantification of marrow osteoblasts and CAR cells, measurement of SDF-1 (CXCL12), IL-6, BAFF, assessment of myeloma cell proliferation and survival in bone marrow

  14 days after last drug treatment

• Response rate as defined by the International Myeloma Working Group (IMWG) criteria

  14 days after last drug treatment

• Overall survival duration of patients treated on study

  1 year

• Progression-free survival of patients treated on study

  1 year

• Duration of response of patients treated on study

  1 year

Study Arms (1)

Arm 1

EXPERIMENTAL

Filgrastim 5 ug/kg from Day -3 to Day 10 of a single cycle. Bortezomib will be given at the patient's current dose on Days 1, 4, 8, and 11 OR Carfilzomib will be given at the patient's current dose on Days 1, 2, 8, 9, 15, and 16 OR IMID will be given at the patient's current dose once daily on Days 1-21. Patients receiving an IMID (thalidomide, lenalidomide, or pomalidomide) as part of a bortezomib or carfilzomb regimen should continue the same scheduled as the current regimen. Dexamethasone should be continued at the same dose and schedule as the patient's current regimen. PO cyclophosphamide should be continued at the same dose and schedule as the patient's current regimen.

Drug: Filgrastim; Drug: Bortezomib; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Cyclophosphamide; Drug: Thalidomide; Drug: Lenalidomide; Drug: Pomalidomide

Interventions

Filgrastim DRUG

Also known as: G-CSF, Neupogen®, Granulocyte Colony-Stimulating Factor

Arm 1

Bortezomib DRUG

Also known as: Velcade®

Arm 1

Carfilzomib DRUG

Also known as: Kyprolis®

Arm 1

Dexamethasone DRUG

Arm 1

Cyclophosphamide DRUG

Also known as: Cytoxan

Arm 1

Thalidomide DRUG

Also known as: Thalomid

Arm 1

Lenalidomide DRUG

Also known as: Revlimid

Arm 1

Pomalidomide DRUG

Also known as: Pomalyst

Arm 1

Eligibility Criteria

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

You may qualify if:

• Patient must have a confirmed diagnosis of multiple myeloma. The patient may be any stage of multiple myeloma. The patient may have received one or more lines of prior therapy (there is no limit to number of prior lines of therapy permissible).
• Patient must be ≥18 years of age
• Patient must be in active treatment with one of the following:
• twice-weekly bortezomib (on Days 1, 4, 8, and 11 of a 21-day cycle) with or without dexamethasone
• carfilzomib (on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle) with or without dexamethasone
• an IMID with or without dexamethasone daily on Days 1 to 21.
• Patients being treated with bortezomib or carfilzomb may also be receiving an IMID or PO cyclophosphamide with the regimen.
• Patient must have shown stable or progressive disease on the current bortezomib-, carfilzomib-, or IMID-containing regimen with a measurable monoclonal protein component in the serum (at least 0.5 g/dl on electrophoresis or 0.05 g/dl \[50mg/dl\] on serum-free-light-chain). Patients who had an initial response on the current bortezomib-, carfilzomib-, or IMID-containing regimen but now have stable (plateaued) disease are eligible.
• Patient must have an ECOG performance status of 0 - 2
• Patient must be receiving concurrent treatment with bisphosphonates, with one dose occurring within 30 days prior to first day (Day -3) of protocol treatment
• Patient must have acceptable hematologic parameters, defined as:
• Absolute neutrophil count \> 1000 cells/mm3
• Platelets ≥ 50,000 cells/mm3
• Hemoglobin ≥ 8 g/dl
• Patient must have adequate liver function, defined as:

You may not qualify if:

• Patient must not be receiving any agents with known or suspected anti-myeloma activity (other than bortezomib, carfilzomib, dexamethasone, an IMID or PO cyclophosphamide, and bisphosphonates with the current regimen)
• Patient must not be actively using myeloid growth factors
• Patient must not have had any prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
• Patient must not have any uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, and symptomatic heart failure
• Patient must not have neuropathy ≥ grade 3 or painful neuropathy ≥ grade 2 (NCI CTCAE v 4.0)
• Patient must not have any known active infections requiring IV antibiotic, antiviral, or antifungal therapy
• Patient must not be pregnant or breastfeeding

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Bortezomib; carfilzomib; Dexamethasone; Cyclophosphamide; Thalidomide; Lenalidomide; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ravi Vij, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: February 23, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 26, 2015

Record last verified: 2015-01

Locations

US (1)