Phase I Study of Bortezomib With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma

NCT02220608 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 2014120261KL2TR002346-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the highest dose of a drug called bortezomib that can be given with a drug called G-CSF before stem cell collection to help in the mobilization of stem cells.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; G-CSF; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of bortezomib when given with G-CSF

  The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first 28 days after administration of the first dose of bortezomib and before auto-HSCT. Dose escalations will proceed until the MTD has been reached.

  Approximately 12 months (completion of all patients on trial)

Study Arms (2)

Arm 1: Dose Level 1 (Bortezomib & G-CSF)

EXPERIMENTAL

G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of \> 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.

Biological: Bortezomib; Drug: G-CSF

Arm 2: Dose Level 2 (Bortezomib & G-CSF)

EXPERIMENTAL

G-CSF will be administered daily for 5 days (Days 1-5). On Day 4 at approximately 1800 hours, bortezomib will be administered. Apheresis will begin on Day 5 either 15 or 18 hours following Day 4 bortezomib dose; 20L of peripheral blood will be processed with a cumulative target collection goal of \> 6.0x106 CD34+cells/kg. If the target collection goal is not met after one apheresis procedures, up to three additional days of G-CSF and apheresis may be repeated.

Biological: Bortezomib; Drug: G-CSF

Interventions

Bortezomib BIOLOGICAL

Also known as: Velcade, LDP 341, MLN341, PS-341

Arm 1: Dose Level 1 (Bortezomib & G-CSF); Arm 2: Dose Level 2 (Bortezomib & G-CSF)

G-CSF DRUG

Also known as: Neupogen, filgrastim XM02, granulocyte colony-stimulating factor, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, tbo-filgrastim, tevagrastim

Arm 1: Dose Level 1 (Bortezomib & G-CSF); Arm 2: Dose Level 2 (Bortezomib & G-CSF)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of multiple myeloma.
• Eligible for autologous transplantation.
• Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-12 months of the first dose of initial therapy.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Platelets ≥ 50,000/mm3
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥1,000/mm3
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Total bilirubin ≤ 1.5 x IULN
• Measured or calculated creatinine clearance ≥ 30 mL/min
• Female patients who:
• are postmenopausal for at least 1 year before the screening visit OR
• are surgically sterile OR

You may not qualify if:

• Previous stem cell collection or transplantation (autologous or allogeneic).
• Evidence of multiple myeloma disease progression (as defined by IMWG) any time prior to auto-HSCT.
• Diagnosis of plasma cell leukemia.
• Concurrent hematologic or non-hematologic malignancy requiring treatment (other than multiple myeloma or secondary amyloidosis).
• Radiation therapy within 3 weeks prior to enrollment.
• Grade 2 or higher peripheral neuropathy.
• Known hypersensitivity to any of the following: bortezomib, boron, mannitol.
• Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or serious medical or psychiatric illness/social situations that would limit compliance with study requirements.
• Female patients who are pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 14 days of study entry.
• Known HIV-positivity. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients with HIV-positivity when indicated.
• Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of the trial and throughout the duration of the trial

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• Ghobadi A, Holt M, Ritchey J et al. The effect of Bortezomib (B) Alone or in Combination with Other Agents for Stem Cell Mobilization in Mice. Blood (ASH Annual Meeting Abstracts), Nov 2012; 120: 583

  BACKGROUND

• Ghobadi A, Fiala MA, Rettig M, Schroeder M, Uy GL, Stockerl-Goldstein K, Westervelt P, Vij R, DiPersio JF. A Phase I Study of the Safety and Feasibility of Bortezomib in Combination With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Oct;19(10):e588-e593. doi: 10.1016/j.clml.2019.04.017. Epub 2019 May 2.

  PMID: 31358485 DERIVED

Related Links

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

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Granulocyte Colony-Stimulating Factor; Filgrastim

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)

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

Study Officials

• Armin Ghobadi, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 15, 2014
• First Posted: August 20, 2014
• Study Start: February 20, 2015
• Primary Completion: July 31, 2016
• Study Completion: November 30, 2016
• Last Updated: January 8, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)