Panobinostat and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

NCT ID: NCT00962507

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-01-31

Brief Summary

RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving panobinostat together with everolimus may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with everolimus in treating patients with relapsed or refractory lymphoma or multiple myeloma.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the safety and feasibility of combining panobinostat with everolimus in patients with recurrent or refractory lymphoma or multiple myeloma.
• To define the maximum tolerated dose of panobinostat in combination with everolimus in these patients.

Secondary

• To obtain preliminary data for response to this treatment regimen in these patients.
• To perform correlative studies relevant to this treatment regimen.

OUTLINE: This is a dose-escalation study of panobinostat.

Patients receive oral panobinostat 3 days a week and oral everolimus once every other day for 4 weeks Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples may be collected for pharmacokinetic and correlative laboratory studies.

After completion of study treatment, patients are followed up for ≥ 4 weeks.

Conditions

Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

everolimus

Beginning with 5 mg every other day Monday, Wednesday or Friday for a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment.

Intervention Type: DRUG

panobinostat

10 mg every Monday and Thursday of a 28 day cycle. Dose escalation will be determined by the toxicities associated with treatment.

Intervention Type: DRUG

laboratory biomarker analysis

Pre-study, day 1 and day 26 samples to evaluation how the study drugs work in vitro (in a test tube).

Intervention Type: OTHER

pharmacological study

Pre-study, day 1 and day 26

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:

• Hodgkin or non-Hodgkin lymphoma (including small lymphocytic lymphoma [SLL])

• Any histology, including B, T, or NK/T cell allowed
• Multiple myeloma (MM)
• Relapsed or refractory disease

• Patients with lymphoma must have relapsed after or be refractory to an upfront regimen (e.g., CHOP or ABVD) and a salvage regimen (e.g., ICE or ESHAP)

• Patients with SLL should have relapsed after a fludarabine-containing regimen
• Patients with MM must have progressed within 100 days after receiving a regimen containing bortezomib and either thalidomide or lenalidomide AND have a 25% increase in serum paraproteins, urinary light chains, or plasma cell number in the bone marrow
• No active CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³ (transfusion allowed in patients with biopsy-proven bone marrow involvement)
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to leukemic involvement)
• Serum bilirubin ≤ 1.5 times ULN
• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• Serum potassium normal
• Serum phosphorous normal
• Serum total calcium (corrected for serum albumin) or serum ionized calcium normal
• Serum magnesium normal
• TSH and free T4 normal (thyroid hormone replacement allowed)
• Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤ 2.5 times ULN (elevated levels allowed provided an appropriate lipid-lowering medication has been initiated)
• LVEF normal by MUGA or ECHO
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method (including barrier method) contraception during and for 3 months after completion of study treatment
• No impaired cardiac function, including any of the following:

• QTc > 450 msec by screening ECG
• Congenital long QT syndrome
• History of sustained ventricular tachycardia
• History of ventricular fibrillation or torsades de pointes
• Bradycardia, defined as heart rate (HR) < 50 beats/min (pacemaker allowed provided HR ≥ 50 beats/min)
• Myocardial infarction or unstable angina within the past 6 months
• NYHA class III-IV congestive heart failure
• Right bundle branch block and left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension
• No unresolved diarrhea > CTCAE grade 1
• No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• No other concurrent severe or uncontrolled medical condition
• No other primary malignancy within the past 5 years other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
• No known HIV or hepatitis C positivity
• No significant history of non-compliance to medical regimens
• No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or temsirolimus), or their excipients

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior autologous or allogeneic stem cell transplantation allowed
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
• More than 1 week since prior and no concurrent immunization with live attenuated vaccines
• More than 4 weeks since prior valproic acid
• No other prior histone deacetylase inhibitors
• No concurrent chronic systemic corticosteroids or another immunosuppressive agent, other than for control of itching (as in cutaneous T-cell lymphoma)

• Concurrent corticosteroids allowed provided patient has been on a stable dosage regimen for ≥ 2 weeks before study entry
• Topical or inhaled corticosteroids allowed
• No concurrent drugs that may induce torsades de pointes
• No concurrent CYP3A4 inhibitors
• No concurrent radiotherapy or other anticancer therapy
• No concurrent grapefruit, grapefruit juice, or seville (sour) oranges
• No concurrent medications that may cause QTc prolongation
• No other concurrent investigational therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leslie Popplewell, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

City of Hope Medical Group

Pasadena, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-08099

Identifier Type: REGISTRY

Identifier Source: secondary_id

NOVARTIS-CHNMC-08099

Identifier Type: -

Identifier Source: secondary_id

CDR0000652208

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2010-00259

Identifier Type: REGISTRY

Identifier Source: secondary_id

08099

Identifier Type: -

Identifier Source: org_study_id