Overview

This trial is active, not recruiting.

Conditions follicular lymphoma, marginal zone lymphoma
Treatments azacitidine, lenalidomide
Phase phase 2
Sponsor Duke University
Collaborator Celgene Corporation
Start date April 2010
End date March 2014
Trial size 11 participants
Trial identifier NCT01121757, Pro00019069

Summary

The purpose of this study is to evaluate the response and safety in subjects receiving the drugs lenalidomide and azacitidine when each drug is given by itself and when the drugs are taken together. This study is open for patients with relapsed or refractory follicular or marginal zone lymphoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Azacitidine 75 mg/m2 subcutaneously (SC) or IV on days 1-5; subjects will begin Part 2 at the azacitidine dose level tolerated in Part 1a. Lenalidomide dose is 15mg po per day on days 1-21; starting dose during Part 2 will depend upon how well the subject tolerated drug during Part 1.
azacitidine Vidaza
Azacitidine 75 mg/m2 SC or IV on days 1-5; subjects will begin Part 2 at the azacitidine dose level tolerated in Part 1a.
lenalidomide Revlimid
Lenalidomide dose is 15mg po per day on days 1-21; starting dose during Part 2 will depend upon how well the subject tolerated drug during Part 1.

Primary Outcomes

Measure
Response Predicted by Molecular Signatures, and True Response Rate
time frame: Response will be assessed after 4 cycles of single agent and after 6 cycles of the combination.
Overall Response
time frame: Response will be assessed after at least 4 months on first study drug.
Overall Response
time frame: Response will be assessed after at least 4 months on second drug.
Overall Response
time frame: Response will be assessed after at least 6 months on combination drug.

Secondary Outcomes

Measure
Number of Participants With Grade 3 and 4 Toxicities
time frame: While taking the study drug and 30 days after the last dose

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histologically or cytologically confirmed Follicular or Marginal Zone Lymphoma 2. Refractory disease defined as persistence of evaluable disease after therapy or have relapsed disease to at least one prior treatment regimen 3. Understand and voluntarily sign an informed consent form 4. Age > or = to 18 years 5. Able to adhere to the study requirements 6. A frozen tumor sample must be available for microarray analysis. This may either be a previously collected sample if it was properly prepared or a new biopsy may be obtained. o At least 1 core biopsy specimen using at least a 16 gauge needle, which corresponds to roughly 25 mg of tissue. An equivalent amount of biopsy material from previously performed procedures, as long as it was fresh frozen, can be used. Sample obtained with leukapheresis is acceptable in subjects with a white blood cell count (WBC) of 100,000 or greater. 7. Eastern Cooperative Oncology Group (ECOG) performance status of < or = to 2 8. Laboratory test results within ranges specified by the protocol. 9. Disease free of prior malignancies for > or = to 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast or superficial melanoma only requiring excision or prostate cancer with a prostate specific antigen (PSA) that has not increased for at least 3 months. 10. All study participants must be willing to be registered into the mandatory RevAssist® program, and comply with the requirements of RevAssist®. 11. Females of childbearing potential (FCBP) must comply with pregnancy testing requirements. Men and women must use approved birth control methods during the study. 12. Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. 13. If at high risk for thrombotic event (such as on steroids or history of deep vein thrombosis), subjects must be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid may use warfarin or low molecular weight heparin) Exclusion Criteria: 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). 3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study 4. Use of any other experimental drug or therapy within 28 days of baseline. 5. Known hypersensitivity to thalidomide or mannitol. 6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs 7. Any prior use of lenalidomide or azacitidine 8. Concurrent use of other anti-cancer agents or treatments 9. Known positive for HIV or infectious hepatitis, type B or C 10. No chemotherapy, biologics or immunotherapy within 2 weeks prior to registration as specified in the protocol. Subjects must have recovered from all therapy-related non-hematological toxicities to < grade 1 or to baseline if patient started with > grade 1 toxicity. There is no time limit with regards to radiation prior to registration. 11. No radioimmunotherapy within 2 months prior to registration. Subjects must have recovered from all therapy-related toxicities to < grade 1 or to baseline if patient started with > grade 1 toxicity. 12. No prior allogeneic stem cell transplantation unless allogeneic engraftment is <2% 13. Subjects receiving chronic, systemic treatment with corticosteroids equivalent to >20mg of prednisone per day

Additional Information

Official title A Phase 2 Study Evaluating the Efficacy of Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma
Principal investigator Anne W. Beaven, MD
Description This will be a prospective, non-randomized, un-blinded, phase 2 efficacy trial using an Immunomodulatory derivatives of thalidomide (IMiD™)compound and a hypomethylating agent for epigenetic targeted therapies in patients with relapsed/refractory follicular and marginal zone lymphoma. There will be two parts to the trial. Each patient will progress through each part of the study. Part 1: Sequential single agent therapy with azacitidine and lenalidomide. Each agent will be given for four-six 28-day cycles. Subjects with less than a complete response (CR) after 4 cycles of study drug in Part 1a or 1b 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. There will be no washout period required between Part 1 and Part 2. Part 2: Combination therapy with azacitidine and lenalidomide given in 28-day cycle for up to 13 cycles in subjects who have stable disease or better.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Duke University.