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

September 14, 2023 updated by: Sherif Farag, MB, BS

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

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.

Study Overview

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)

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46219
        • IU Health Central Indiana Cancer Centers
      • Indianapolis, Indiana, United States, 46256
        • Community Regional Cancer Center
      • Lafayette, Indiana, United States, 47904
        • IU Health Arnett Cancer Center
    • Michigan
      • Wyoming, Michigan, United States, 49519
        • Metro Health Cancer Care
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Seidman Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.

Phase I component:

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

Phase I and II components:

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

Phase I and II components:

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

Phase II component:

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

Phase II component:

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.
Time Frame: From C1D1 up to a maximum of 7 months or until death
In the first phase, MTD of bendamustine was determined in combination with bortezomib and pegylated liposomal doxorubicin to gain a better idea of safe dosing before proceeding with the second phase to assess efficacy. Assuming myelosuppression being a dose-limiting effect that could have been overcome with growth factor support, MTD of the combination with myeloid growth factor support was also tested.
From C1D1 up to a maximum of 7 months or until death
Phase II : Overall Response Rate
Time Frame: From C1D1 up to a maximum of 52 months or until death
Overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin was assessed in patients with relapsed or refractory Multiple Myeloma. Per modified International Myeloma Working Group criteria: Complete Response (CR) : Negative for monoclonal protein by immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow ; PR : 50% or more reduction in serum M-protein and 90% or more reduction in urine M-protein or to <200 mg/24hours or a 50% or more reduction in free light chain level ; Overall Response (OR) = CR +PR.
From C1D1 up to a maximum of 52 months or until death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I & Phase II : Toxicity of Treatment Regimen
Time Frame: From C1D1 until death or up to a maximum of 54 months
Toxicity profile (for all patients) were presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined.
From C1D1 until death or up to a maximum of 54 months
Phase II : Time to Progression
Time Frame: From C1D1 up to a maximum of 54 months or until death

The time from the start of treatment (i.e., first dose) of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin to disease progression, with disease progression and death due to disease progression as events and deaths due to causes other than progression as censored. Censoring date will be the last disease evaluation date for patient without progression/death or date of death due to other diseases for patients' deaths due to other causes.Per modified International Myeloma Working Group criteria: Progressive disease (PD) is reported if any one of the following criteria is met:

Increase of 25% or more in serum or urine M-protein from baseline;Serum M-protein and/or the absolute increase must be ≥0.5 g/dL;Urine M-protein and/or absolute increase must be ≥200 mg/24 hours ; Development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas;Development of hyperc.

From C1D1 up to a maximum of 54 months or until death
Phase II: Progression-free Survival (PFS)
Time Frame: From C1D1 up to a maximum of 54 months until death

The time from the start of treatment of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin. to disease progression or death (regardless of cause of death), whichever comes first. Censoring date will be the last disease evaluation date.Per modified International Myeloma Working Group criteria: Progressive disease (PD) is reported if any one of the following criteria is met:

Increase of 25% or more in serum or urine M-protein from baseline;Serum M-protein and/or the absolute increase must be ≥0.5 g/dL;Urine M-protein and/or absolute increase must be ≥200 mg/24 hours ; Development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas;Development of hyperc.

From C1D1 up to a maximum of 54 months until death
Phase II: Duration of Survival
Time Frame: From C1D1 up to a maximum of 52 months
Duration of MM patients treated with bendamustine, bortezomib and pegylated liposomal doxorubicin. from first date of at least partial response to the time of progression or death due to disease progression as events, with disease progression and death due to disease progression as events and deaths due to causes other than progression as censored. Censoring date will be the last disease evaluation date or date of death due to other causes as appropriate.
From C1D1 up to a maximum of 52 months
Phase II: Overall Survival
Time Frame: From C1D1 up to a maximum of 54 months or until death
The time from the start of treatment to death from any cause with last date known alive as censoring date.
From C1D1 up to a maximum of 54 months or until death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Sherif Farag, M.B., B.S., Hoosier Cancer Research Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

August 5, 2010

First Submitted That Met QC Criteria

August 6, 2010

First Posted (Estimated)

August 9, 2010

Study Record Updates

Last Update Posted (Actual)

October 6, 2023

Last Update Submitted That Met QC Criteria

September 14, 2023

Last Verified

September 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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