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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01177683
First Posted: August 9, 2010
Last Update Posted: July 26, 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:
Hoosier Cancer Research Network
Cephalon
Information provided by (Responsible Party):
Sherif Farag, MB, BS, Hoosier Cancer Research Network
  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: Intervention Model: Single Group Assignment
Masking: None (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: Hoosier Cancer Research Network MM08-141

Resource links provided by NLM:


Further study details as provided by Sherif Farag, MB, BS, Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Assessing Patient Response to Bendamustine - Phase I by assessing patient adverse events [ Time Frame: 6 months ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 2017
Estimated Primary Completion Date: October 2017 (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

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:

  • 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
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): NCT01177683


Locations
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
IU Health Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
IU Health Arnett Cancer Center
Lafayette, Indiana, United States, 47904
United States, Michigan
Metro Health Cancer Care
Wyoming, Michigan, United States, 49519
United States, Ohio
University Hospitals Seidman Cancer Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Sherif Farag, MB, BS
Hoosier Cancer Research Network
Cephalon
Investigators
Study Chair: Sherif Farag, M.B., B.S. Hoosier Cancer Research Network
  More Information

Additional Information:
Responsible Party: Sherif Farag, MB, BS, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01177683     History of Changes
Other Study ID Numbers: MM08-141
First Submitted: August 5, 2010
First Posted: August 9, 2010
Last Update Posted: July 26, 2017
Last Verified: July 2017

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
Liposomal doxorubicin
Bortezomib
Bendamustine Hydrochloride
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents