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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01121757
First received: February 11, 2010
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Follicular Lymphoma
Marginal Zone Lymphoma
Drug: azacitidine
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study Evaluating the Efficacy of Epigenetic Modulation in Relapsed/Refractory Follicular Lymphoma and Marginal Zone Lymphoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Response predicted by molecular signatures, and true response rate [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using a modified version of the revised response criteria for malignant lymphoma by Cheson et al. 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.

  • Overall response [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using a modified version of the revised response criteria for malignant lymphoma by Cheson et al. 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.


Secondary Outcome Measures:
  • Serum markers measured on the first day of cycle 1 and on the first day of cycle 3 [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: While taking the study drug and 30 days after the last dose ] [ Designated as safety issue: Yes ]
    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

  • Response predicted by molecular signature, immune response-1 and immune response 2, true response [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ] [ Designated as safety issue: No ]
  • Response to either of the drugs given alone, response to either one or both of the single agents [ Time Frame: Within 4 months of taking single agent and 6 months of taking the combination ] [ Designated as safety issue: No ]
    Response and progression will be evaluated in this study using a modified version of the revised response criteria for malignant lymphoma by Cheson et al. 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.


Enrollment: 11
Study Start Date: April 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine and Lenalidomide

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.

Drug: azacitidine
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.
Other Name: Vidaza
Drug: lenalidomide
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.
Other Name: Revlimid

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01121757

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Celgene Corporation
Investigators
Principal Investigator: Anne W. Beaven, MD Duke University Medical Center Durham, NC USA
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01121757     History of Changes
Other Study ID Numbers: Pro00019069
Study First Received: February 11, 2010
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
relapsed
refractory
lymphoma
follicular
marginal zone

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Azacitidine
Lenalidomide
Thalidomide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances

ClinicalTrials.gov processed this record on July 22, 2014