Status:
TERMINATED
Epigenetic Modulation in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Lead Sponsor:
Anne Beaven, MD
Collaborating Sponsors:
Novartis
Conditions:
Diffuse Large B-cell Lymphoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
The purpose of this study is evaluate the response, safety and tolerability in subjects receiving the investigational drugs, RAD001 and LBH589. Subjects in Part 1 will receive one drug for four cycles...
Detailed Description
This will be a prospective, non-randomized, un-blinded phase 2 efficacy trial using a mechanistic target of rapamycin (mTOR) inhibitor and a histone deacetylase (HDAC) inhibitor for epigenetic targete...
Eligibility Criteria
Inclusion
- de novo or transformed Diffuse large B cell non-Hodgkin lymphoma (DLBCL). DLBCL-like lymphomas allowed:
- Epstei-Barr virus (EBV)+ DLBCL in elderly,
- DLBCL with chronic inflammation,
- Primary cutaneous DLBCL, leg type,
- B cell lymphoma unclassifiable - between DLBCL and Burkitt lymphoma,
- B cell lymphoma unclassifiable - between large B cell lymphoma and classical Hodgkin lymphoma,
- Anaplastic lymphoma kinase (ALK)+ large B cell lymphoma,
- T cell histiocyte rich large B cell lymphoma
- Primary mediastinal B cell lymphoma
- Follicular grade 3 B cell lymphoma
- Refractory or relapsed disease to \>/= 1 prior treatment regimen: should include autologous stem cell transplant unless patient refused or ineligible.
- Age \> 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status \<2.
- Measurable or evaluable disease by physical exam, radiographs or bone marrow involvement
- Frozen tumor or paraffin-embedded sample available.
- 3-4 core fresh/fresh-frozen biopsy specimens available. Leukapheresis may be done for patients with leukocytosis.
- Laboratory Values per protocol.
Exclusion
- Laboratory Values
- Grade 3 hyperlipidemia (Serum cholesterol \>400mg/dl or serum triglycerides \>5 x ULN)
- Serum Glucose \> 250mg/dl on \>/= 2 checks on 2 separate days
- Diabetics accepted if sugars controlled
- Unlimited prior chemotherapy regimens, however:
- No prior exposure to RAD001 or LBH589 or drugs that target mTOR (sirolimus, temsirolimus, etc) or HDAC (vorinostat)
- No valproic acid during study or 5 days preceding start of first drug
- No chemotherapy, biologics or immunotherapy \< 2 weeks before registration (6 weeks if last received bis-chloroethylnitrosourea (BCNU) or mitomycin C). Subjects must be recovered from therapy-related non-hematological toxicities to \< grade 1 or baseline if started with \> grade 1 toxicity.
- No time limit for radiation prior to registration.
- No radioimmunotherapy \< 2 months prior to registration. Subjects must be recovered from therapy-related toxicities to \< grade 1 or baseline if started with \> grade 1 toxicity.
- No prior allogeneic stem cell transplantation unless allogeneic engraftment is \<2%.
- Subjects receiving chronic, systemic treatment with corticosteroids = to \>20mg of prednisone per day.
- Subjects receiving replacement for adrenal insufficiency allowed.
- Topical or inhaled corticosteroids allowed.
- History of other primary malignancy \< 3 years ago, except inactive basal, squamous cell carcinoma of the skin or superficial melanoma only requiring excision, prostate cancer with a prostate specific antigen (PSA) stable for \>/=3 months, carcinoma in situ of cervix.
- Major surgery \< 4 weeks before or Minor surgery \< 2 weeks before registration. Subjects must be recovered from toxicities to \< grade 1 or baseline if started with \> grade 1 toxicity.
- Investigational drugs \< 4 weeks prior to registration.
- Impaired Cardiac Function per protocol.
- Pregnant or breastfeeding females or adults of reproductive potential not using effective birth control
- Diffusing capacity or transfer factor of the lung for carbon monoxide (DLCO) \< 40% if tested (per protocol).
- Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse Oximetry.
- Immunization with live attenuated vaccines \< 1 week of study entry
- Impaired GI function or GI disease that may alter absorption of RAD001 or LBH589
- Concurrent severe \&/or uncontrolled medical conditions
- Medications with risk of prolonging QT interval or inducing torsade de pointes or interacting with LBH589 and RAD001 may be used per the protocol.
- Active bleeding tendency
- Positive for HIV.
- Positive for Hepatitis C virus (HCV).
- History of non-compliance to medical regimens.
Key Trial Info
Start Date :
February 1 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2016
Estimated Enrollment :
50 Patients enrolled
Trial Details
Trial ID
NCT00978432
Start Date
February 1 2012
End Date
March 1 2016
Last Update
November 25 2016
Active Locations (1)
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1
Duke University Medical Center
Durham, North Carolina, United States, 27710