Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00967044
First received: August 25, 2009
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

Objectives:

Primary:

  • Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of the novel combination of everolimus + Panobinostat (LBH589) in a phase-I study in patients with relapsed lymphoma (Hodgkin and non-Hodgkin).
  • Determine the safety and efficacy of this novel combination in a phase-II study in patients with relapsed Hodgkin and non-Hodgkin lymphoma

Secondary:

  • Determine the in vivo effect of therapy on selected serum cytokines/chemokines (TGF-beta, thymus and activation-regulated chemokine (TARC), IL-6, IL-10, VEGF).
  • Examine pre-treatment level of selected molecular targets (HDACs 1-11, STAT6, pSTAT6, STAT3, pSTAT3, Myc, Akt, Pichia anomala killer toxin (pAkt), S6, pS6, p21, cyclin D1) in primary lymphoma cells and the surrounding reactive inflammatory cells obtained by core needle biopsies from patients with relapsed lymphoma.
  • Examine the correlation between molecular and biologic markers and clinical response and/or treatment-related toxicity.

Condition Intervention Phase
Lymphoma
Drug: Panobinostat
Drug: Everolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II of Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) and Dose Limiting toxicity (DLT) of Everolimus with Panobinostat [ Time Frame: 28 day treatment cycle ] [ Designated as safety issue: Yes ]
    MTD highest dose at which no more than 1 in 6 of the patients in the cohort experiences one or more DLTs in the first treatment cycle.


Enrollment: 31
Study Start Date: November 2009
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panobinostat + Everolimus
Panobinostat (LBH589) Plus Everolimus (RAD001)
Drug: Panobinostat
Starting dose of 10 mg by mouth per day, self-administered (by patients), 3 x per week
Other Name: LBH589
Drug: Everolimus
Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.
Other Names:
  • Afinitor
  • RAD001

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed Hodgkin or non Hodgkin's lymphoma
  2. Relapsed or refractory after standard treatments and with no curative option with conventional therapy
  3. No evidence of cerebral or meningeal involvement by lymphoma
  4. Age >= 18 years
  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  6. Life expectancy of at least 3 months
  7. Signed informed consent form prior to enrollment
  8. Patients must meet the following laboratory criteria: Aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and ALT/serum glutamate pyruvate transaminase (SGPT) </= 2.5 x upper limit of normal (ULN) ) or </= 5.0 x ULN if the transaminase elevation is due to lymphoma involvement, Serum bilirubin </= 1.5 x ULN, Serum creatinine </=1.5 x ULN free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement)
  9. Patients must have at least one measurable site of disease
  10. Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) >/= 1.0 x 109/L, Platelets >/=100 x 109/L
  11. Fasting serum cholesterol </=300 mg/dL OR </=7.75 mmol/L AND fasting triglycerides </= 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication 24 hours before starting therapy.
  12. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study drug

Exclusion Criteria:

  1. Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)
  2. Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study
  3. Previous radioimmunotherapy within 12 weeks
  4. Prior therapy with HDAC or [1] mammalian target of rapamycin (mTOR) inhibitors i.e. temsirolimus, vorinostat (the list is not inclusive of investigational agents in these classes of drugs)
  5. Patient with known HIV infection
  6. Known active viral hepatitis
  7. Any serious active disease or co-morbid condition, which in the opinion of the principle investigator, will interfere with the safety or with compliance with the study
  8. Impaired cardiac function including any one of the following: • Screening ECG with a corrected QT interval (QTc) > 450 msec confirmed by the investigator prior to enrollment to the study • Patients with congenital long QT syndrome • History of sustained ventricular tachycardia • Any history of ventricular fibrillation or torsades de pointes • Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate >= 50 beats per minute are eligible.
  9. Impaired cardiac function including any one of the following continued: • Patients with a myocardial infarction or unstable angina within 6 months from registration on study • Congestive heart failure (NY Heart Association class III or IV) • Right bundle branch block and left anterior hemiblock (bifascicular block) • Uncontrolled hypertension
  10. Concomitant use of drugs with a risk of causing torsades de pointes
  11. Patients with unresolved diarrhea Common Toxicity Criteria for Adverse Effects (CTCAE) grade 1
  12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral PANOBINOSTAT or everolimus.
  13. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception.
  14. Male patients whose sexual partners are WOCBP not using effective birth control
  15. Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, basal or squamous cell carcinoma of the skin, or early stage prostate carcinoma.
  16. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  17. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  18. Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone <= 20 mg. Topical or inhaled corticosteroids are allowed.
  19. Patients should not receive immunization with attenuated live vaccines within one week of study registration or during study period
  20. Chronic obstructive pulmonary disease (COPD) or asthma requiring therapy
  21. Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
  22. Active (acute or chronic) uncontrolled severe infection, requiring oral or intravenous antibiotics.
  23. Patients receiving treatment on another clinical research trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967044

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Yasuhiro Oki, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00967044     History of Changes
Other Study ID Numbers: 2008-0805, NCI-2011-03023
Study First Received: August 25, 2009
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Relapsed or Refractory Lymphoma
Hodgkin's lymphoma
Non Hodgkin's Lymphoma
NHL
LBH589
Panobinostat
RAD001
Everolimus

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Everolimus
Sirolimus
Panobinostat
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014