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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00962507

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

42.1

Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Multiple Myeloma and Plasma Cell Neoplasm	Drug: everolimus Drug: panobinostat Other: laboratory biomarker analysis Other: pharmacological study	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Evaluating the Combination of the Deacetylase Inhibitor, LBH589 Plus the mTOR Inhibitor RAD001, in Relapsed and Refractory Adult Patients With Lymphoma

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Jan 1, 2013

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose [90 days post treatment start]
Toxicity [90 days post treatment start]

Secondary Outcome Measures

Pharmacokinetic and correlative studies [Day 1 and Day 26 of the first cycle of treament]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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