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

NCT01121757 | Terminated Phase 2 Results

• 1 other identifier: Pro00019069
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Follicular Lymphoma; Marginal Zone Lymphoma

Keywords

relapsed; refractory; lymphoma; follicular; marginal zone

Outcome Measures

Primary Outcomes (4)

• Response Predicted by Molecular Signatures Compared to 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).

  approximately one year

• Overall Response

  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.

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

• Overall Response

  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.

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

• Overall Response

  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.

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

Secondary Outcomes (1)

• Number of Participants With Grade 3 and 4 Toxicities

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

Other Outcomes (1)

• Serum Markers Measured on the First Day of Cycle 1 and on the First Day of Cycle 3

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

Study Arms (2)

Azacitidine followed by Lenalidomide

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.

Drug: azacitidine; Drug: lenalidomide

Lenalidomide followed by Azacitidine

EXPERIMENTAL

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 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.

Drug: azacitidine; Drug: lenalidomide

Interventions

azacitidine DRUG

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.

Also known as: Vidaza

Azacitidine followed by Lenalidomide; Lenalidomide followed by Azacitidine

lenalidomide DRUG

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.

Also known as: Revlimid

Azacitidine followed by Lenalidomide; Lenalidomide followed by Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed Follicular or Marginal Zone Lymphoma
• Refractory disease defined as persistence of evaluable disease after therapy or have relapsed disease to at least one prior treatment regimen
• Understand and voluntarily sign an informed consent form
• Age \> or = to 18 years
• Able to adhere to the study requirements
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of \< or = to 2
• Laboratory test results within ranges specified by the protocol.
• 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.
• All study participants must be willing to be registered into the mandatory RevAssist® program, and comply with the requirements of RevAssist®.
• Females of childbearing potential (FCBP) must comply with pregnancy testing requirements. Men and women must use approved birth control methods during the study.
• 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.
• 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)

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
• 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
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide or mannitol.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Any prior use of lenalidomide or azacitidine
• Concurrent use of other anti-cancer agents or treatments
• Known positive for HIV or infectious hepatitis, type B or C
• 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.
• 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.
• No prior allogeneic stem cell transplantation unless allogeneic engraftment is \<2%
• Subjects receiving chronic, systemic treatment with corticosteroids equivalent to \>20mg of prednisone per day

Sponsors & Collaborators

• Duke University: lead
• Celgene: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Recurrence; Lymphoma

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Anne Beaven, MD, Associate Professor
• Organization: Duke University Health Center

anne.beaven@duke.edu

9196848964

Study Officials

• Anne W. Beaven, MD

  Duke University Medical Center Durham, NC USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: May 12, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: January 1, 2016
• Last Updated: September 12, 2016
• Results First Posted: May 7, 2015

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)