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

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Bendamustine

Doxorubicin

Bortezomib

Bendamustine

Filgrastim

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Indiana University Melvin and Bren Simon Cancer Center
IU Health Central Indiana Cancer Centers
Community Regional Cancer Center
IU Health Arnett Cancer Center
Metro Health Cancer Care
University of Rochester Medical Center
University Hospitals Seidman Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.

Outcomes

Primary Outcome Measures

Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.

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.

Phase II : Overall Response Rate

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.

Secondary Outcome Measures

Phase I & Phase II : Toxicity of Treatment Regimen

Toxicity profile (for all patients) were presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined.

Phase II : Time to Progression

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.

Phase II: Progression-free Survival (PFS)

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.

Phase II: Duration of Survival

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.

Phase II: Overall Survival

The time from the start of treatment to death from any cause with last date known alive as censoring date.

Full Information

NCT ID

NCT01177683

First Posted

August 5, 2010

Last Updated

September 14, 2023

Sponsor

Sherif Farag, MB, BS

Collaborators

Hoosier Cancer Research Network, Cephalon, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01177683

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Lack of accrual

Study Start Date

July 2010 (undefined)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sherif Farag, MB, BS

Collaborators

Hoosier Cancer Research Network, Cephalon, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Intervention Description

Phase I component: Bendamustine escalating cohorts to determine MTD, IV over 1 hour, Days 1 and 4

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Intervention Description

Phase I and II components: Pegylated liposomal doxorubicin, 30 mg/m2 IV over 1 hour, Day 4

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Intervention Description

Phase I and II components: Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Intervention Description

Phase II component: Bendamustine at at MTD IV over 1 hour, Days 1 and 4

Intervention Type

Drug

Intervention Name(s)

Filgrastim

Intervention Description

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

Primary Outcome Measure Information:

Title

Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.

Description

Time Frame

From C1D1 up to a maximum of 7 months or until death

Title

Phase II : Overall Response Rate

Description

Time Frame

From C1D1 up to a maximum of 52 months or until death

Secondary Outcome Measure Information:

Title

Phase I & Phase II : Toxicity of Treatment Regimen

Description

Toxicity profile (for all patients) were presented by rate of overall toxicity and rates of grade 3 or 4 toxicities analyzed separately and combined.

Time Frame

From C1D1 until death or up to a maximum of 54 months

Title

Phase II : Time to Progression

Description

Time Frame

From C1D1 up to a maximum of 54 months or until death

Title

Phase II: Progression-free Survival (PFS)

Description

Time Frame

From C1D1 up to a maximum of 54 months until death

Title

Phase II: Duration of Survival

Description

Time Frame

From C1D1 up to a maximum of 52 months

Title

Phase II: Overall Survival

Description

The time from the start of treatment to death from any cause with last date known alive as censoring date.

Time Frame

From C1D1 up to a maximum of 54 months or until death

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Hoosier Cancer Research Network

Official's Role

Study Chair

Facility Information:

Facility Name

Indiana University Melvin and Bren Simon Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

IU Health Central Indiana Cancer Centers

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46219

Country

United States

Facility Name

Community Regional Cancer Center

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46256

Country

United States

Facility Name

IU Health Arnett Cancer Center

City

Lafayette

State/Province

Indiana

ZIP/Postal Code

47904

Country

United States

Facility Name

Metro Health Cancer Care

City

Wyoming

State/Province

Michigan

ZIP/Postal Code

49519

Country

United States

Facility Name

University of Rochester Medical Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

University Hospitals Seidman Cancer Center

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44106

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.hoosieroncologygroup.org

Description

Hoosier Oncology Group Homepage

Learn more about this trial

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

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