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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01177683
• Other study ID #: MM08-141
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 2010
• Est. completion date: December 2017

Study information

• Verified date: September 2023
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bendamustine
Phase I component: Bendamustine escalating cohorts to determine MTD, IV over 1 hour, Days 1 and 4
• Doxorubicin
Phase I and II components: Pegylated liposomal doxorubicin, 30 mg/m2 IV over 1 hour, Day 4
• Bortezomib
Phase I and II components: Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11
• Bendamustine
Phase II component: Bendamustine at at MTD IV over 1 hour, Days 1 and 4
• Filgrastim
Phase II component: Filgrastim (if defined in MTD) 5 µg/kg/day SC, starting day 6 until neutrophil recovery to ANC >1000

Locations

Country	Name	City	State
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Community Regional Cancer Center	Indianapolis	Indiana
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	IU Health Central Indiana Cancer Centers	Indianapolis	Indiana
United States	IU Health Arnett Cancer Center	Lafayette	Indiana
United States	University of Rochester Medical Center	Rochester	New York
United States	Metro Health Cancer Care	Wyoming	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Sherif Farag, MB, BS	Cephalon, Inc., Hoosier Cancer Research Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From C1D1 up to a maximum of 7 months or until death
Primary	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.	From C1D1 up to a maximum of 52 months or until death
Secondary	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.	From C1D1 until death or up to a maximum of 54 months
Secondary	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.	From C1D1 up to a maximum of 54 months or until death
Secondary	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.	From C1D1 up to a maximum of 54 months until death
Secondary	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.	From C1D1 up to a maximum of 52 months
Secondary	Phase II: Overall Survival	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

External Links

•   Hoosier Oncology Group Homepage