Trial Outcomes & Findings for Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma (NCT NCT01121757)

Last Updated: 2016-09-12

Results Overview

The predicted response (response to therapy vs. no response to therapy) using gene sequencing will be compared to the overall "true" response (reported in Primary Outcome 2).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

approximately one year

Results posted on

2016-09-12

Participant Flow

Patients were recruited from June 2010 through January 2012 from the Duke Cancer Institute.

The first 3 patients started on 1a and the next 3 patients started in 1b and the next 3 were in 1a and so on. Eleven subjects consented to the study, 1 patient elected other treatment options prior to assignment and 1 other patient converted to Diffuse Large B-Cell Lymphoma, which made them ineligible.

Participant milestones

Participant milestones
Measure	1a-Azacitidine Followed by Lenalidomide Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
First Drug STARTED	6	3
First Drug COMPLETED	5	1
First Drug NOT COMPLETED	1	2
Second Drug STARTED	4	1
Second Drug COMPLETED	4	1
Second Drug NOT COMPLETED	0	0
Combination STARTED	2	1
Combination COMPLETED	0	0
Combination NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	1a-Azacitidine Followed by Lenalidomide Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
First Drug Death	1	0
First Drug Disease Progression	0	2
Combination Physician Decision	0	1
Combination Disease Progression	2	0

Baseline Characteristics

Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1a-Azacitidine Followed by Lenalidomide n=6 Participants Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a complete remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=3 Participants Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a complete remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Age, Categorical >=65 years	3 Participants n=99 Participants	1 Participants n=107 Participants	4 Participants n=206 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	1 Participants n=107 Participants	5 Participants n=206 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=99 Participants	3 Participants n=107 Participants	9 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	6 Participants n=99 Participants	3 Participants n=107 Participants	9 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	6 participants n=99 Participants	3 participants n=107 Participants	9 participants n=206 Participants

PRIMARY outcome

Timeframe: approximately one year

Population: The number of participants who were evaluated for a response were analyzed to see if the prediction of response vs. no response through gene expression matched the true response.

The predicted response (response to therapy vs. no response to therapy) using gene sequencing will be compared to the overall "true" response (reported in Primary Outcome 2).

Outcome measures

Outcome measures
Measure	1a-Azacitidine Followed by Lenalidomide n=6 Participants Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=3 Participants Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
Response Predicted by Molecular Signatures Compared to True Response Predicted: Response; Actual: Response	1 participants	0 participants
Response Predicted by Molecular Signatures Compared to True Response Predicted: No Response; Actual: No Response	2 participants	3 participants
Response Predicted by Molecular Signatures Compared to True Response Predicted: Response; Actual: No Response	3 participants	0 participants

PRIMARY outcome

Timeframe: Response will be assessed after at least 4 months on first study drug.

Population: Everyone who started the first drug regimen

Number of patients with a complete or partial response using Cheson criteria for lymphoma. A complete response is defined as a complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy. A partial response is defined as a greater than or equal to 50% decrease in the sum of the products of the greatest diameters of 6 largest dominant nodes or nodal masses. No increase in size of nodes, liver or spleen and no new sites of disease. Patients who have been on study drug for at least 2 months will be considered evaluable for response as long as they have had repeat imaging to assess response or clear progression based on physical exam.

Outcome measures

Outcome measures
Measure	1a-Azacitidine Followed by Lenalidomide n=6 Participants Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=3 Participants Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
Overall Response	1 participants	0 participants

PRIMARY outcome

Timeframe: Response will be assessed after at least 4 months on second drug.

Population: Everyone who started the second drug regimen

Outcome measures

Outcome measures
Measure	1a-Azacitidine Followed by Lenalidomide n=4 Participants Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=1 Participants Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
Overall Response	2 participants	0 participants

PRIMARY outcome

Timeframe: Response will be assessed after at least 6 months on combination drug.

Population: Only subjects that completed combination drug will be included in analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: While taking the study drug and 30 days after the last dose

Evaluate the safety of lenalidomide, azacitidine and the combination of azacitidine + lenalidomide in patients with lymphoma; grading the adverse events using Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0

Outcome measures

Outcome measures
Measure	1a-Azacitidine Followed by Lenalidomide n=6 Participants Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=3 Participants Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a Complete Remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
Number of Participants With Grade 3 and 4 Toxicities Grade 3	5 participants	3 participants
Number of Participants With Grade 3 and 4 Toxicities Grade 4	1 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Within 4 months of taking single agent and 6 months of taking the combination

Outcome measures

Outcome data not reported

Adverse Events

1a-Azacitidine Followed by Lenalidomide

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

1b-Lenalidomide Followed by Azacitidine

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1a-Azacitidine Followed by Lenalidomide n=6 participants at risk Subjects will take azacitidine for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a complete remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of azacitidine (first drug) will proceed to receive lenalidomide (second drug) for 4-6 cycles. Subjects with a CR after lenalidomide may receive up to 6 cycles of lenalidomide and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.	1b-Lenalidomide Followed by Azacitidine n=3 participants at risk Subjects will take lenalidomide for 4-6 cycles (first drug) followed by a 1-6 week washout period. Subjects with a complete remission (CR) may receive up to 6 cycles of first drug and will not receive the next until disease progression. Subjects with less than a CR after 4 cycles of lenalidomide (first drug) will proceed to receive azacitidine (second drug) for 4-6 cycles. Subjects with a CR after azacitidine may receive up to 6 cycles of azacitidine and will not start on the combination drug until disease progression. The combination therapy (azacitidine and lenalidomide) will be given in 28-day cycles for up to 13 cycles in subjects who have stable disease or better.
Blood and lymphatic system disorders Anemia	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Infections and infestations Cellulitis (left lower extremity)	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Investigations Thrombocytopenia	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy (Breast Cancer)	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy (Cecal adenocarcinoma )	0.00% 0/6 • We collect adverse event information from the time they start drug until 30 days after the last dose.	33.3% 1/3 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy (Refractory Anemia with Excess blasts-1)	16.7% 1/6 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.	0.00% 0/3 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Nervous system disorders Syncope	0.00% 0/6 • We collect adverse event information from the time they start drug until 30 days after the last dose.	33.3% 1/3 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • We collect adverse event information from the time they start drug until 30 days after the last dose.	33.3% 1/3 • Number of events 1 • We collect adverse event information from the time they start drug until 30 days after the last dose.

Other adverse events

Additional Information

Anne Beaven, MD, Associate Professor

Duke University Health Center

Phone: 9196848964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place