Clinical trial NCT01177683: 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
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Hoosier Cancer Research Network
name: Cephalon, Inc.
First posted: 2010-08-09
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

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.

Primary outcomes:
measure: Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.
timeFrame: From C1D1 up to a maximum of 7 months or until death
measure: Phase II : Overall Response Rate
timeFrame: From C1D1 up to a maximum of 52 months or until death
Secondary outcomes:
measure: Phase I & Phase II : Toxicity of Treatment Regimen
timeFrame: From C1D1 until death or up to a maximum of 54 months
measure: Phase II : Time to Progression
timeFrame: From C1D1 up to a maximum of 54 months or until death
measure: Phase II: Progression-free Survival (PFS)
timeFrame: From C1D1 up to a maximum of 54 months until death
measure: Phase II: Duration of Survival
timeFrame: From C1D1 up to a maximum of 52 months
measure: Phase II: Overall Survival
timeFrame: From C1D1 up to a maximum of 54 months or until death
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: IU Health Central Indiana Cancer Centers
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: IU Health Arnett Cancer Center
state: Indiana
city: Wyoming
country: United States
facility: Metro Health Cancer Care
state: Michigan
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center
state: Ohio
Study officials:
affiliation: Hoosier Cancer Research Network
name: Sherif Farag, M.B., B.S.
role: STUDY_CHAIR
References: