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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bortezomib
G-CSF
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, G-CSF, Bortezomib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
    • Women of childbearing potential and men must agree to practice 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • 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

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

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

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

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
August 15, 2014
Last Updated
January 4, 2018
Sponsor
Washington University School of Medicine
Collaborators
Millennium Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02220608
Brief Title
Phase I Study of Bortezomib With G-CSF for Stem Cell Mobilization in Patients With Multiple Myeloma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
February 20, 2015 (Actual)
Primary Completion Date
July 31, 2016 (Actual)
Study Completion Date
November 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Millennium Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The purpose of this phase I study is to define the maximum tolerated dose of bortezomib and its mobilization effects when given with G-CSF for stem cell mobilization in multiple myeloma patients. We hypothesize that bortezomib, in addition to increasing the number of mobilized stem cells, will optimize final apheresis product by decreasing myeloma cell contamination. Therefore, all multiple myeloma patients rather than multiple myeloma patients with G-CSF mobilization failure will be the target of this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, G-CSF, Bortezomib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Dose Level 1 (Bortezomib & G-CSF)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2: Dose Level 2 (Bortezomib & G-CSF)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade, LDP 341, MLN341, PS-341
Intervention Type
Drug
Intervention Name(s)
G-CSF
Other Intervention Name(s)
Neupogen, filgrastim XM02, granulocyte colony-stimulating factor, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, tbo-filgrastim, tevagrastim
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of bortezomib when given with G-CSF
Description
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.
Time Frame
Approximately 12 months (completion of all patients on trial)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Women of childbearing potential and men must agree to practice 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armin Ghobadi, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
Citation
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
Results Reference
background
PubMed Identifier
31358485
Citation
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.
Results Reference
derived
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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