Study of Vorinostat With Doxil and Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01492881
• Date of registration: 12/12/2011
• Primary sponsor: UNC Lineberger Comprehensive Cancer Center
• Public title: Study of Vorinostat With Doxil and Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma
• Scientific title: A Multi-Center, Single-Arm, Phase II Study of Vorinostat (V) in Combination With Pegylated Liposomal Doxorubicin (PLD) and Bortezomib (B) Followed by VB Maintenance in Patients With Relapsed and Relapsed/Refractory Multiple Myeloma
• Date of first enrolment: April 2012
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: http://clinicaltrials.gov/show/NCT01492881
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Peter M Voorhees, MD
• Affiliation: Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill

Key inclusion & exclusion criteria

Inclusion Criteria:

Relapsed or relapsed and refractory multiple myeloma:

- Relapsed MM is defined as clinically active disease, in patients who have received
one or more prior therapies, that is not refractory to the most recent treatment.
(Refractory to the prior treatment means either progressive disease (PD) on last
prior therapy; best response of stable disease (SD) to last prior therapy, or PD
within 60 days of completing therapy).

- Relapsed and refractory MM is defined as relapsed disease, which either becomes
non-responsive while on salvage therapy, or progresses within 60 days of last
therapy.

1 to 3 prior lines of therapy for multiple myeloma (a single line of treatment may
consist of 1 or more agents and regimens. A single line of therapy may be most
easily delineated by a response to treatment followed by a change in treatment due to
the progression of disease.

- Prior bortezomib- and anthracycline-based therapy is allowed; prior cumulative
doxorubicin dose must be <360 mg/m2 (or its equivalent)

- Prior autologous stem cell transplantation is allowed provided the patient is 3
months out from transplant and has recovered from any transplant-related toxicities
(to baseline or grade 1 in severity)

All prior treatment-related non-hematologic toxicities resolved to =Grade 1 (or baseline),
not including alopecia

Prior radiation therapy completed =2 weeks prior to day 1 of treatment Eastern Cooperative
Oncology Group (ECOG) performance status of 0-2

Age =18 years

Life expectancy of at least 6 months

Adequate bone marrow function (without platelet or RBC transfusion support within one week
of screening) as demonstrated by:

- Hemoglobin = 8 g/dL (use of erythropoietin stimulating agent is OK)

- Absolute neutrophil count (ANC) = 1,000 cells/mm3 (without granulocyte growth factor
support)

- Platelet count = 100,000/mm3 (=75,000/mm3 in patients with =30% marrow involvement of
MM who are felt to have thrombocytopenia primarily due to marrow infiltration of
disease as opposed to diminished marrow reserves from prior therapy)

Adequate hepatic and renal function as demonstrated by:

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x upper
limit of normal (ULN)

- Total serum bilirubin =1.5 x ULN

- Creatinine clearance (CrCL) = 30mL/min as measured via Cockcroft-Gault or 24-hour
urine testing

Documented negative serologic testing for hepatitis B (HBV) and Hepatitis C (HCV) as
measured by the following (NOTE: this testing is not necessary if patient has had negative
testing within the last year, and no subsequent risk factors for acquisition of these
viruses):

- HBV surface antigen, surface antibody, and core antibody (NOTE: patients who are
seropositive because of hepatitis B vaccine are eligible)

- HCV antibody.

- For patients with serologic evidence of viral hepatitis, quantitative PCR will be
performed.

Documented negative HIV blood test (NOTE: this testing is not necessary if patient has had
negative testing within the last year, and no subsequent risk factors for acquisition of
this virus)

Adequate cardiac function, defined as:

- No EKG evidence of acute ischemia

- No EKG evidence of active clinically significant conduction system abnormalities

- No EKG evidence of > Grade 2 (>480 ms) QTc prolongation

- Prior to study entry, any ECG abnormality at screening not felt to put the patient at
risk has to be documented by the investigator as not medically significant

- No uncontrolled angina or severe ventricular arrhythmias

- No clinically significant pericardial disease

- No history of myocardial infarction within the last 6 months

- Left ventricular ejection fraction (LVEF) must be > 45% by either echocardiography or
radionuclide-based multiple gated acquisition (MUGA)

- No Class II or higher New York Heart Association Congestive Heart Failure

Negative serum ß-hCG pregnancy test within 72 hours of day 1 of treatment with study
medications in women of child-bearing potential

All males and females of childbearing potential must agree to use an effective
contraceptive method during the study and for 3 months following the last dose of study
treatment. Effective contraception is defined as any medically recommended method (or
combination of methods) as per standard of care, including abstinence. Females of
non-childbearing potential are those who are postmenopausal greater than 1 year or who
have had a bilateral tubal ligation or hysterectomy

Exclusion Criteria:

- > 3 prior lines of therapy for treatment of MM

Receipt of prior allogeneic stem cell/bone marrow transplantation

Primary refractory MM as defined by the ASH/FDA Workshop on Clinical Endpoints in Multiple
Myeloma[24]

Peripheral neuropathy (PN) = grade 1 with pain or =grade 2 PN within 14 days prior to
enrollment

Known history of HIV, HBV or HCV infection

Serum potassium =3.0 mmol/L or serum magnesium =1.6mg/dL that cannot be corrected with
supplementation

Known hypersensitivity to bortezomib or any of its components (boron, mannitol),
vorinostat, doxorubicin, or any of the components of PLD; Patients with a history of
reactions to other liposomal drug formulations will be evaluated individually, and if
their reactions were felt to have been due to the liposome itself, as opposed to the
encapsulated agent, they will be excluded at the discretion of the investigators.

Prior or concomitant use of a histone deacetylase inhibitor (exception: prior valproic
acid for epilepsy is allowed provided patient undergoes a 30 day wash out prior to D1 of
study treatment)

No major surgery within 3 weeks prior to day 1 of study treatment

Active, serious infection, medical, or psychiatric condition that would represent an
inappropriate risk to the patient or would likely compromise achievement of the primary
study objective

Other prior or concomitant malignancies with the exception of:

- Non-melanoma skin cancer

- In-situ malignancy

- Low-risk prostate cancer after curative therapy

- Other cancer for which the patient has been disease free for = 3 years

Pregnant or lactating women



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Multiple Myeloma

Intervention(s)

Drug: Bortezomib

Drug: pegylated liposomal doxorubicin

Drug: Vorinostat

Primary Outcome(s)

Estimate the overall response rate. [Time Frame: 18 months]

Secondary Outcome(s)

Assess the safety and tolerability. [Time Frame: 18 months]

Estimate Progression-free survival [Time Frame: 36 months]

Estimate the overall survival. [Time Frame: 36 months]

Evaluate the quality of life measures in patients. [Time Frame: 18 months]

Secondary ID(s)

LCCC 1119

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck