NCT00967044

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P50-P75 for phase_1 lymphoma

Timeline
Completed

Started Nov 2009

Typical duration for phase_1 lymphoma

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 25, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 27, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

November 1, 2009

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
6 months until next milestone

Results Posted

Study results publicly available

September 10, 2014

Completed
Last Updated

February 26, 2015

Status Verified

February 1, 2015

Enrollment Period

4.3 years

First QC Date

August 25, 2009

Results QC Date

September 2, 2014

Last Update Submit

February 9, 2015

Conditions

Lymphoma

Keywords

Relapsed or Refractory LymphomaHodgkin's lymphomaNon Hodgkin's LymphomaNHLLBH589PanobinostatRAD001Everolimus

Outcome Measures

Primary Outcomes (1)

  • Maximum Tolerated Dose (MTD) of Everolimus With Panobinostat

    MTD of the novel combination of Everolimus + Panobinostat (LBH589) in a phase-I study in participants with relapsed lymphoma (Hodgkin and non-Hodgkin) where MTD is defined as the highest dose at which no more than 1 in 6 of the participants in the cohort experiences one or more dose limiting toxicities (DLTs) in the first 28 day treatment cycle. Thirty patients were enrolled onto four dose levels: Everolimus (mg, orally) 5, 5, 10, 10 daily or Panobinostat (mg, orally) 10, 20, 20, 30 three times per week. The MTD was established without the use of colony stimulating factor in cycle 1.

    28 day treatment cycle

Study Arms (1)

Panobinostat + Everolimus

EXPERIMENTAL

Panobinostat (LBH589) Plus Everolimus (RAD001)

Drug: PanobinostatDrug: Everolimus

Interventions

PanobinostatDRUG

Starting dose of 10 mg by mouth per day, self-administered (by patients), three times per week

Also known as: LBH589
Panobinostat + Everolimus
EverolimusDRUG

Starting dose of 5 mg every day by mouth with 1 cup (8 ounces) of water, in morning after eating a low-fat meal.

Also known as: Afinitor, RAD001
Panobinostat + Everolimus

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Burkitt's lymphoma, Lymphoblastic lymphoma, Chronic lymphocytic leukemia (Small lymphocytic lymphoma may be included)
  • Chemotherapy or radiation therapy or other investigational agents within 4 weeks prior to entering the study
  • Previous radioimmunotherapy within 12 weeks
  • 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)
  • Patient with known HIV infection
  • Known active viral hepatitis
  • 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
  • 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.
  • 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
  • Concomitant use of drugs with a risk of causing torsades de pointes
  • Patients with unresolved diarrhea Common Toxicity Criteria for Adverse Effects (CTCAE) grade 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral PANOBINOSTAT or everolimus.
  • 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.
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • 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.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

MeSH Terms

Conditions

LymphomaRecurrenceHodgkin DiseaseLymphoma, Non-Hodgkin

Interventions

PanobinostatEverolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic AcidsHydroxylaminesAminesOrganic ChemicalsHydroxy AcidsCarboxylic AcidsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsSirolimusMacrolidesLactones

Limitations and Caveats

Initially intended to proceed to phase II at MTD, treatment interruptions were frequently required in participants treated at MTD for Grade 3/4 Thrombocytopenia so study amended to obtain more detailed safety data at MTD in expanded phase I study.

Results Point of Contact

Title
Yasuhiro Oki, MD / Assistant Professor, Lymphoma/Myeloma
Organization
University of Texas MD Anderson Cancer Center
CR_Study_Registration@mdanderson.org
713-792-2860

Study Officials

  • Yasuhiro Oki, MD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 25, 2009

First Posted

August 27, 2009

Study Start

November 1, 2009

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

February 26, 2015

Results First Posted

September 10, 2014

Record last verified: 2015-02

Locations

US(1)