Epigenetic Modulation in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

This study has been terminated.
(The toxicity seemed to outweigh the benefit.)
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Anne Beaven, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00978432
First received: September 15, 2009
Last updated: April 27, 2016
Last verified: April 2016
Results First Received: March 17, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Diffuse Large B-cell Lymphoma
Interventions: Drug: RAD001
Drug: LBH589
Drug: Doublet (RAD001 and LBH589)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm 1a (RAD001 Followed by LBH589)

Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles.

Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period.

Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease.

There will be a 1-6 week ‘washout’ period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient’s best interest.

RAD001: 10 mg/day for Part 1 of the trial

LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial

Arm 1b (LBH589 Followed by RAD001)

Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles.

Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period.

Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease.

There will be a 1-6 week ‘washout’ period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient’s best interest.

RAD001: 10 mg/day for Part 1 of the trial

LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial

Doublet (Combination RAD001 and LBH589)

Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily.

Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2.


Participant Flow:   Overall Study
    Arm 1a (RAD001 Followed by LBH589)     Arm 1b (LBH589 Followed by RAD001)     Doublet (Combination RAD001 and LBH589)  
STARTED     10     5     18  
COMPLETED     7     4     13  
NOT COMPLETED     3     1     5  
Withdrawal by Subject                 0                 0                 1  
Lack of Efficacy                 1                 1                 3  
Adverse Event                 2                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm 1a (RAD001 Followed by LBH589)

Part 1a: Sequential single agent therapy with RAD001 and LBH589. Each agent will be given for four-six 28-day cycles.

Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period.

Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease.

There will be a 1-6 week ‘washout’ period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient’s best interest.

RAD001: 10 mg/day for Part 1 of the trial

LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial

Arm 1b (LBH589 Followed by RAD001)

Part 1b: Sequential single agent therapy with LBH589 and RAD001 . Each agent will be given for four-six 28-day cycles.

Subjects with less than a CR after 4 cycles of study drug should proceed to the next study drug(s) after the prescribed washout period.

Subjects with a CR may receive up to 6 cycles of study drug and will not receive the next study drug(s) until there is evidence of progressive disease.

There will be a 1-6 week ‘washout’ period between stopping and starting each agent in Part 1, unless rapid progression suggests holding therapy would not be in the patient’s best interest.

RAD001: 10 mg/day for Part 1 of the trial

LBH589: 40 mg on Monday, Wednesday and Friday weekly for Part 1 of the trial

Doublet (Combination RAD001 and LBH589)

Subjects will receive the doublet of RAD001 and LBH589 given in two to thirteen, 28-day cycles. Subjects will be evaluated for the disease status after completion of cycle two and then after every 4 cycles. Subjects with progressive disease will stop after 2 cycles. Subjects with stable disease or better may receive up to 13 cycles. LBH589 will start at 15mg po three days a week at least 2 days apart such as on days M/W/F or T/Th/Sat and RAD001 will start at 7.5mg po daily.

Doublet (RAD001 and LBH589): RAD001 7.5 mg by mouth daily and LBH589 15 mg by mouth on Monday/Wednesday/Friday during Part 2.

Total Total of all reporting groups

Baseline Measures
    Arm 1a (RAD001 Followed by LBH589)     Arm 1b (LBH589 Followed by RAD001)     Doublet (Combination RAD001 and LBH589)     Total  
Number of Participants  
[units: participants]
  10     5     18     33  
Age  
[units: participants]
       
<=18 years     0     0     0     0  
Between 18 and 65 years     5     2     9     16  
>=65 years     5     3     9     17  
Gender  
[units: participants]
       
Female     6     1     3     10  
Male     4     4     15     23  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     0     0     0     0  
Not Hispanic or Latino     10     5     18     33  
Unknown or Not Reported     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     1     0     1     2  
White     9     5     17     31  
More than one race     0     0     0     0  
Unknown or Not Reported     0     0     0     0  
Region of Enrollment  
[units: participants]
       
United States     10     5     18     33  



  Outcome Measures
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1.  Primary:   Overall Response Rate   [ Time Frame: after 2 cycles of each study drug or after 2 cycles of doublet, up to 24 weeks ]

2.  Primary:   Assessment of Association Between Observed Response to RAD001 and LBH589 and the Response Predicted by Molecular Signatures Developed in Our Pre-clinical Model   [ Time Frame: From the start of combination therapy until a maximum of 2 years after completion of therapy ]

3.  Secondary:   Summary of Adverse Events (AEs)   [ Time Frame: From the time of first dose of study drug until 4 weeks after participant has stopped study drug; up to 1 year ]

4.  Secondary:   Distribution of Change Across Time of mTOR and HDAC-I Inhibition From Baseline Until After the 1st 2 Cycles of Study Drug in Patients Who Received LBH and RAD.   [ Time Frame: after 2 cycles of study therapy; up to 8 weeks ]

5.  Secondary:   Evaluate the Association of Observed Response to the Doublet With the Response Predicted by Molecular Signatures for Activated B Cell Like (ABC) DLBCL and for Germinal Center B Cell Like (GCB) DLBCL.   [ Time Frame: up to 13 cycles of therapy; approximately 1 year ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Anne Beaven, MD
Organization: Duke University Medical Center
phone: 919-684-8964
e-mail: anne.beaven@duke.edu



Responsible Party: Anne Beaven, MD, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00978432     History of Changes
Other Study ID Numbers: Pro00012947
Study First Received: September 15, 2009
Results First Received: March 17, 2016
Last Updated: April 27, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board