We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00903968
First Posted: May 19, 2009
Last Update Posted: November 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Brigham and Women's Hospital
Genzyme, a Sanofi Company
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Irene Ghobrial, MD, Dana-Farber Cancer Institute
May 18, 2009
May 19, 2009
August 31, 2017
September 29, 2017
November 14, 2017
May 2009
June 2016   (Final data collection date for primary outcome measure)
  • 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.
  • 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.
  • 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).
  • 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).
  • To evaluate the safety of plerixafor and bortezomib in patients with multiple myeloma. [ Time Frame: 3 years ]
  • To identify the maximum tolerated dose of plerixafor and bortezomib. [ Time Frame: 3 years ]
  • To assess the response rate of plerixafor and bortezomib in patients with relapsed or relapsed/refractory multiple myeloma. [ Time Frame: 3 years ]
Complete list of historical versions of study NCT00903968 on ClinicalTrials.gov Archive Site
  • 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
  • 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.
  • To assess time to progression. [ Time Frame: 3 years ]
  • To assess duration of response. [ Time Frame: 3 years ]
  • To assess mobilization of MM cells and other BM microenvironment cells. [ Time Frame: 3 years ]
  • To determine the degree of apoptosis in mobilized MM cells. [ Time Frame: 3 years ]
Not Provided
Not Provided
 
Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma
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.
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Plerixafor
    Other Name: AMD3100
  • Drug: bortezomib
    Other Name: velcade
  • Drug: Dexamethasone
    Other Name: Decadron
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
  • 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.
    Interventions:
    • Drug: Plerixafor
    • Drug: bortezomib
    • Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
58
October 2016
June 2016   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00903968
08-273
Yes
Not Provided
Not Provided
Irene Ghobrial, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
  • Brigham and Women's Hospital
  • Genzyme, a Sanofi Company
  • Millennium Pharmaceuticals, Inc.
Principal Investigator: Irene Ghobrial, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP