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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

Phase 1
18 Years
Not Enrolling
Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

Thank you

Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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

- 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


- 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


- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

90 days post treatment start

Safety Issue:


Principal Investigator

Leslie Popplewell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

January 2013

Related Keywords:

  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • recurrent adult T-cell leukemia/lymphoma
  • adult nasal type extranodal NK/T-cell lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • splenic marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • cutaneous B-cell non-Hodgkin lymphoma
  • Waldenstrom macroglobulinemia
  • refractory multiple myeloma
  • Neoplasms
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma



City of Hope Medical Center Duarte, California  91010
City of Hope Medical Group Pasadena, California  91105