Trial record 1 of 1 for:    MM08-141
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Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoosier Cancer Research Network
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01177683
First received: August 5, 2010
Last updated: August 20, 2014
Last verified: August 2014

August 5, 2010
August 20, 2014
July 2010
December 2015   (final data collection date for primary outcome measure)
  • Assessing Patient Response to Bendamustine - Phase I by assessing patient adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Determine the maximum tolerated dose of bendamustine in association with bortezomib and pegylated liposomal doxorubicin in patients with relapsed or refractory Multiple Myeloma.
  • Overall Response Rate of Treatment Regimen - Phase II by assessing patient response rates [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assess the overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin in patients with relapsed or refractory Multiple Myeloma.
  • Determining the Maximum Tolerated Dose of Bendamustine - Phase I [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Determine the maximum tolerated dose of bendamustine in association with bortezomib and pegylated liposomal doxorubicin in patients with relapsed or refractory Multiple Myeloma.
  • Overall Response Rate of Treatment Regimen - Phase II [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Assess the overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin in patients with relapsed or refractory Multiple Myeloma.
Complete list of historical versions of study NCT01177683 on ClinicalTrials.gov Archive Site
  • Toxicity of Treatment Regimen - Phase I and II by assessing patient adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Describe the toxicity of the combination of bendamustine with bortezomib and pegylated liposomal doxorubicin.
  • Evaluation of Survival - Phase II by assessing patient survival times [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Evaluate the time to progression, overall survival, progression free survival, and duration of response of Multiple Myeloma patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin.
  • Bendamustine Pharmacokinetics - Phase II by evaluating patient samples [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Correlate bendamustine pharmacokinetics parameters (Cmax, t1/2, and AUC) at cycle 1 (and cycle 2) with patients' responses and correlate the DNA damage/repair at day 1 of cycle 1 and day 4 of cycle 2 with patients' responses.
  • Toxicity of Treatment Regimen - Phase I and II [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Describe the toxicity of the combination of bendamustine with bortezomib and pegylated liposomal doxorubicin.
  • Evaluation of Survival - Phase II [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Evaluate the time to progression, overall survival, progression free survival, and duration of response of Multiple Myeloma patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin.
  • Bendamustine Pharmacokinetics - Phase II [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Correlate bendamustine pharmacokinetics parameters (Cmax, t1/2, and AUC) at cycle 1 (and cycle 2) with patients' responses and correlate the DNA damage/repair at day 1 of cycle 1 and day 4 of cycle 2 with patients' responses.
Not Provided
Not Provided
 
Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma
A Phase I/II Trial of Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed or Refractory Multiple Myeloma

This is an open label phase I/II trial to determine the safety and the biologic activity of the bendamustine, bortezomib and pegylated liposomal doxorubicin combination.

Phase I component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine escalating cohorts IV over 1 hour, Days 1 and 4 1 Cycle = 28 days

Phase II component Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11 Doxorubicin 30 mg/m2 IV over 1 hour, Day 4 Bendamustine at MTD IV over 1 hour, Days 1 and 4 Filgrastim (if defined in MTD) 5 µg/kg/day SC, Starting day 6 until neutrophil recovery to ANC >1000

1 Cycle = 28 days; Patients will continue treatment for a total of up to 8 cycles.

ECOG Performance Status: 0-2

Hematopoietic:

  • Absolute neutrophil count (ANC) ≥ 1.2 x K/mm3
  • Platelets ≥ 75 x K/mm3

Hepatic:

  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • AST ≤ 2.5 x ULN
  • ALT ≤ 2.5 x ULN

Renal:

  • Serum creatinine < 3.0 mg/dL

Cardiovascular:

  • LVEF >45% corrected by MUGA scan or echocardiogram.
  • No unstable angina pectoris or recent myocardial infarction (within 6 months)
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Bendamustine

    Phase I component:

    Bendamustine escalating cohorts to determine MTD, IV over 1 hour, Days 1 and 4

  • Drug: Doxorubicin

    Phase I and II components:

    Pegylated liposomal doxorubicin, 30 mg/m2 IV over 1 hour, Day 4

  • Drug: Bortezomib

    Phase I and II components:

    Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11

  • Drug: Bendamustine

    Phase II component:

    Bendamustine at at MTD IV over 1 hour, Days 1 and 4

  • Drug: Filgrastim

    Phase II component:

    Filgrastim (if defined in MTD) 5 µg/kg/day SC, starting day 6 until neutrophil recovery to ANC >1000

Experimental: Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
Interventions:
  • Drug: Bendamustine
  • Drug: Doxorubicin
  • Drug: Bortezomib
  • Drug: Bendamustine
  • Drug: Filgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
69
December 2015
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • A histologically established diagnosis of multiple myeloma with evidence of relapse or refractory disease.
  • Must have a detectable serum or urine M-Protein by protein electrophoresis that is at least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light chain level >100 mg/l for the involved free light chain.
  • Must have received at least one (1) prior line of systemic treatment that has included either lenalidomide or thalidomide.
  • Must be willing to provide correlative blood samples.

Exclusion Criteria:

  • Must not have received an excessive cumulative dose of anthracycline
  • No ≥ grade 2 peripheral neuropathy.
  • No cytotoxic chemotherapy within 30 days prior to registration for protocol therapy.
  • No autologous stem cell transplant within 6 months prior to registration for protocol therapy
  • No prior radiation therapy to > 25% of bone marrow forming bones (i.e., pelvis) within 30 days prior to registration for protocol therapy. See Study Procedures Manual to calculate percent of prior radiation.
  • No current corticosteroid therapy in doses greater than 10 mg daily of prednisone (or equivalent) if given for management of co-morbid conditions.
  • No known central nervous system involvement by myeloma.
  • No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social climate that in the opinion of the investigator would limit compliance with study requirements.
  • No patients known to be positive for HIV, or active Hepatitis A, B, or C.
  • No major surgery within 30 days prior to registration for protocol therapy. Placement of a venous access device within 30 days prior to registration for protocol therapy is allowed.
Both
18 Years and older
No
Contact: Sherif Farag, M.B., B.S. ssfarag@iupui.edu
Contact: Cynthia Burkhardt 317.921.2050 cyburkha@iupui.edu
United States
 
NCT01177683
MM08-141
Yes
Hoosier Cancer Research Network
Hoosier Cancer Research Network
Cephalon
Study Chair: Sherif Farag, M.B., B.S. Hoosier Cancer Research Network
Hoosier Cancer Research Network
August 2014

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