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Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma

This study is currently recruiting participants.
Verified May 2013 by Hoosier Oncology Group
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Hoosier Oncology Group
ClinicalTrials.gov Identifier:
NCT01177683
First received: August 5, 2010
Last updated: May 16, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
 Drug: Bendamustine
Drug: Doxorubicin
Drug: Bortezomib
Drug: Filgrastim
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 69
Study Start Date: July 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.
 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

Detailed Description:

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)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01177683

Contacts
Contact: Sherif Farag, M.B., B.S. ssfarag@iupui.edu
Contact: Cynthia Burkhardt 317.921.2050 cyburkha@iupui.edu

Locations
United States, Indiana
Cancer Care Center of Southern Indiana Withdrawn
Bloomington, Indiana, United States, 47403
IU Health Goshen Hospital Recruiting
Goshen, Indiana, United States, 46527
Contact: Alex Starodub, M.D.     574-535-2886     astarodub@iuhealth.org    
Contact: Rebecca Eickhoff, R.N.     574.364.2649        
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Sherif Farag, M.B., B.S.     317-274-0843     ssfarag@iupui.edu    
Contact: Kerry Bridges     317-274-2552     kdbridge@iupui.edu    
Community Regional Cancer Center Recruiting
Indianapolis, Indiana, United States, 46256
Contact: Anuj Agarwala, M.D.     317-621-7104        
Contact: Lisa McVicker, R.N.     317-621-7104        
IU Health Central Indiana Cancer Centers Recruiting
Indianapolis, Indiana, United States, 46219
Contact: Hillary Wu, M.D.     317-964-5253     hwu@iuhealth.org    
Contact: Yvonne LaFary, R.N.     317.964.5253     ylafary@iuhealth.org    
IU Health Arnett Cancer Center Recruiting
Lafayette, Indiana, United States, 47904
Contact: Thomas Jones, M.D.     765-448-7500        
Contact: Janice Welty, R.N.     765-448-7500     weltyj@iuhealth.org    
Floyd Memorial Cancer Center of Indiana Withdrawn
New Albany, Indiana, United States, 47150
United States, Michigan
Metro Health Cancer Care Recruiting
Wyoming, Michigan, United States, 49519
Contact: Michael Zakem, D.O.     616-252-8100     michael.zakem@metrogr.org    
Contact: Carmen Heaney     616.252.8100     carmen.heaney@metrogr.org    
United States, Ohio
University Hospitals Seidman Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Erica Campagnaro, D.O.     216-844-5884     erica.campagnaro@uhhospitals.org    
Contact: Sherrie Reynolds     216-844-3854     Sherrie.Reynolds@uhhospitals.org    
Sponsors and Collaborators
Hoosier Oncology Group
Cephalon
Investigators
Study Chair: Sherif Farag, M.B., B.S. Hoosier Oncology Group
  More Information

Additional Information:
Hoosier Oncology Group Homepage  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT01177683     History of Changes
Other Study ID Numbers: MM08-141
Study First Received: August 5, 2010
Last Updated: May 16, 2013
Health Authority: United States: Institutional Review Board

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
Doxorubicin
 Bendamustine
Bortezomib
Nitrogen Mustard Compounds
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Protease Inhibitors

ClinicalTrials.gov processed this record on June 18, 2013