Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma

May 19, 2020 updated by: Irene Ghobrial, MD, Dana-Farber Cancer Institute

Phase I/II Trial of Combination Plerixafor (AMD3100) and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma

The purpose of this research study is to determine the safety of plerixafor and bortezomib, and the highest dose that can be given to people safely. Plerixafor appears to stop myeloma cells from attaching to bone marrow and has been used in other phase I studies for mobilization of stem cells for patients with myeloma and lymphoma. We have shown that the combination of plerixafor and bortezomib is very effective in killing myeloma cells in the laboratory more than the effect of each drug alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Hyannis, Massachusetts, United States, 02601
        • Cape Cod Hospital
      • Milford, Massachusetts, United States, 01757
        • Milford Hospital
      • Newton, Massachusetts, United States, 02462
        • Newton-Wellesley Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19124
        • Cancer Treatment Centers of America (Eastern Regional Medical Center)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years of age or older
  • Must have received prior 1-5 therapies for their myeloma and have relapsed or refractory multiple myeloma. Prior therapy with bortezomib is allowed as long as they were not refractory to bortezomib
  • Monoclonal protein serum of 1gm/dL or greater or monoclonal light chain in the urine protein electrophoresis of 200 mg/24 hours or greater, or measurable light chains by free light chain assay of 10 mg/dL or greater, or measurable plasmacytoma
  • ECOG Performance Status 0, 1, or 2
  • Laboratory values as outlined in the protocol

Exclusion Criteria:

  • Uncontrolled infection
  • Cytotoxic chemotherapy < 3 weeks, or biologic or targeted novel therapy < 2 weeks, or corticosteroids < 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma
  • Pregnant women
  • Nursing women
  • Men or women of child-bearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational
  • Known to be HIV positive
  • Radiation therapy < 2 weeks prior to registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I Dose Level 1
Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 2
Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 3
Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 4
Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 5
Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 5B
Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: Phase I Dose Level 6
Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: All Phase I Participants
All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100
Experimental: All Phase II Participants
All Phase I participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
Drug: Dexamethasone
Other Names:
  • Decadron
Drug: bortezomib
Other Names:
  • velcade
Drug: Plerixafor
Other Names:
  • AMD3100

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plerixafor Maximum Tolerated Dose (MTD) [Phase I]
Time Frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of plerixafor was given on days 1, 2, 3, 6, 10, 13 of 21 each cycle.
Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
Bortezomib Maximum Tolerated Dose (MTD) [Phase I]
Time Frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of bortezomib was given on days 3, 6, 10, 13 of 21 each cycle.
Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
Number of Participants With Dose Limiting Toxicity (DLT) [Phase I]
Time Frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
A DLT was defined as (a) grade 3 or greater non-hematologic toxicity, considered by the investigator to be related to plerixafor or bortezomib, with the exception of nausea, vomiting or diarrhea unless receiving maximal medical therapy, (b) grade 4 hematologic toxicity defined as: thrombocytopenia with platelets <10,000 on more than one occasion within first cycle despite transfusion. Grade 4 neutropenia must occur for more than 5 days and/or result in neutropenic fever with elevated temperature (defined as > 101 degrees F). (c) inability to receive Day 1 dose for Cycle 2 due to toxicity. All adverse events were graded according to the CTEP Common Toxicity Criteria (CTCAE v.3.0).
Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.
Response Rate of Plerixafor, Bortezomib, and Dexamethasone in Relapsed or Relapsed/ Refractory Multiple Myeloma (ORR) [Phase I and Phase II]
Time Frame: Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.
Overall response was established based on International Myeloma Working Group (IMWG) criteria with 6 potential categories: Complete Response (CR) which is a complete disappearance of monoclonal paraprotein based on negative immunofixation on the serum M-component and urine M-component and no evidence of myeloma in bone marrow, Very Good Partial Response (VGPR) defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component <100 mg per 24 hours, Partial Response (PR) ≥50% reduction in serum M-component or ≥90% reduction urine M-component or urine M-component <200 mg per 24 hours, Minimal Response (MR) ≥25% reduction in serum or urine M-component, Stable Disease (SD) defined as failure to meet any response criteria, and Progressive Disease (PD) ≥ 25% increase from lowest value reported in serum M-component (absolute ≥0.5 g/dL) and/or urine M-component (absolute ≥200 mg/24 hours).
Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP) [Phase II]
Time Frame: DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.
TTP estimated using the Kaplan-Meier method is defined as the time from registration to progression based on IMWG criteria or date last known progression-free for those who have not progressed. [Durie BG et al. Leukemia. 2006] Progression (PD): ≥ 25% increase from lowest value reported in serum M-component (absolute increase ≥0.5 g/dL) and/or urine M-component (absolute increase ≥200 mg/24 hours); if appropriate, a ≥25% increase above the lowest level in the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); If none of these are measurable then ≥25% increase in bone marrow plasma cell percentage above the lowest response level (absolute ≥10%); Definite development of new bone lesions or soft tissue plasmacytomas OR increase in size of existing
DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.
Duration of Response (DOR) [Phase II]
Time Frame: DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.
DOR is defined as the time from response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died. DOR was estimated using the Kaplan-Meier method.
DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Brigham and Women's Hospital
Genzyme, a Sanofi Company
Millennium Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Irene Ghobrial, MD, Dana-Farber Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2009

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

May 18, 2009

First Submitted That Met QC Criteria

May 18, 2009

First Posted (Estimate)

May 19, 2009

Study Record Updates

Last Update Posted (Actual)

June 2, 2020

Last Update Submitted That Met QC Criteria

May 19, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-273

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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