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

NCT ID: NCT01177683

Last Updated: 2023-10-06

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2017-12-31

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

Phase I component:

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

Doxorubicin

Intervention Type DRUG

Phase I and II components:

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

Bortezomib

Intervention Type DRUG

Phase I and II components:

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

Bendamustine

Intervention Type DRUG

Phase II component:

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

Filgrastim

Intervention Type DRUG

Phase II component:

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

Interventions

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Bendamustine

Phase I component:

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

Intervention Type DRUG

Doxorubicin

Phase I and II components:

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

Intervention Type DRUG

Bortezomib

Phase I and II components:

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

Intervention Type DRUG

Bendamustine

Phase II component:

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

Intervention Type DRUG

Filgrastim

Phase II component:

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoosier Cancer Research Network

OTHER

Sponsor Role collaborator

Cephalon, Inc.

INDUSTRY

Sponsor Role collaborator

Sherif Farag, MB, BS

OTHER

Sponsor Role lead

Responsible Party

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Sherif Farag, MB, BS

Sponsor-Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Sherif Farag, M.B., B.S.

Role: STUDY_CHAIR

Hoosier Cancer Research Network

Locations

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Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Site Status

Community Regional Cancer Center

Indianapolis, Indiana, United States

Site Status

IU Health Arnett Cancer Center

Lafayette, Indiana, United States

Site Status

Metro Health Cancer Care

Wyoming, Michigan, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

University Hospitals Seidman Cancer Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.hoosieroncologygroup.org

Hoosier Oncology Group Homepage

Other Identifiers

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MM08-141

Identifier Type: -

Identifier Source: org_study_id

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