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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: September 29, 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
  Purpose
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.

Condition Intervention Phase
Multiple Myeloma Drug: Plerixafor Drug: bortezomib Drug: Dexamethasone Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Combination Plerixafor (AMD3100) and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Irene Ghobrial, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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.

  • 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.

  • 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 II] [ Time Frame: Disease was assessed for response every cycle on treatment. ]
    Overall response was established based on International Myeloma Working Group (IMWG) criteria with 6 potential categories: Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD), and Progressive Disease (PD).


Secondary Outcome Measures:
  • Time to Progression (TTP) [Phase II] [ Time Frame: DIsease was assessedto document progression every cycle on treatment and post-treatment every 12 weeks until progression. ]
    TTP is defined as the time to progression (time from registration to progression, censored at date last known progression-free for those who have not progressed). This is estimated using the Kaplan-Meier method.

  • 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.


Enrollment: 58
Study Start Date: May 2009
Study Completion Date: October 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
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: Plerixafor
Other Name: AMD3100
Drug: bortezomib
Other Name: velcade
Drug: Dexamethasone
Other Name: Decadron

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00903968


Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Cape Cod Hospital
Hyannis, Massachusetts, United States, 02601
Milford Hospital
Milford, Massachusetts, United States, 01757
Newton-Wellesley Hospital
Newton, Massachusetts, United States, 02462
United States, Pennsylvania
Cancer Treatment Centers of America (Eastern Regional Medical Center)
Philadelphia, Pennsylvania, United States, 19124
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Genzyme, a Sanofi Company
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Irene Ghobrial, MD Dana-Farber Cancer Institute
  More Information

Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00903968     History of Changes
Other Study ID Numbers: 08-273
First Submitted: May 18, 2009
First Posted: May 19, 2009
Results First Submitted: August 31, 2017
Results First Posted: September 29, 2017
Last Update Posted: September 29, 2017
Last Verified: August 2017

Keywords provided by Irene Ghobrial, MD, Dana-Farber Cancer Institute:
refractory
relapsed
bortezomib
AMD3100
plerixafor

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Bortezomib
BB 1101
JM 3100
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents