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Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone in Treating Patients With Previously Untreated Low-Grade Non-Hodgkin Lymphoma

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
cyclophosphamide
dexamethasone
lenalidomide
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring stage I grade 1 follicular lymphoma, contiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I small lymphocytic lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, Waldenstrom macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically confirmed symptomatic non-Hodgkin lymphoma by biopsy within the past 6 months

    • Any of the following subtypes allowed:

      • Grade 1 or 2 lymphoma
      • Small lymphocytic lymphoma
      • Marginal zone lymphoma
      • Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia [WM])
  • Previously untreated disease that, in the investigator's opinion, requires treatment

  • Measurable disease by CT or MRI scans with lymph nodes ≥ 2.0 cm in ≥ 1 dimension

    • WM patients without lymphadenopathy must meet the following criteria:

      • More than 10% lymphocytes, lymphoplasmacytic cells, or plasma cells on a bone marrow aspirate/biopsy
      • Quantitative Immunoglobulin M ≥ 400 mg/dL NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,400/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Creatinine ≤ 2.0 mg/dL
  • Total or direct bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception at least 28 days prior to, during, and for 28 days after completion of study therapy
  • Able to take acetylsalicylic acid (ASA) 325 mg/day as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin)
  • No known hypersensitivity to thalidomide
  • No development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • No myocardial infarction within the past 6 months
  • No other active malignancy requiring treatment, except for localized nonmelanomatous skin cancer or any cancer that, in the judgement of the investigator, has been treated with curative intent and will not interfere with the study treatment plan and response assessment
  • No co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or would interfere significantly with the proper assessment of safety and toxicity of study treatment
  • No known positivity for HIV or infectious hepatitis A, B, or C
  • No serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent
  • Willing to return to Mayo Clinic enrolling institution for follow up
  • Registered into the RevAssist® program and willing and able to comply with the requirements of RevAssist®

PRIOR CONCURRENT THERAPY:

  • No prior lenalidomide
  • No prior irradiation to ≥ 25% of the bone marrow
  • More than 28 days since prior experimental drug or therapy
  • No concurrent radiotherapy, chemotherapy, or immunotherapy
  • No other concurrent anticancer agents or treatments, including thalidomide or investigational agents

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.

Outcomes

Primary Outcome Measures

Assessment of Tumor Response
The proportion of responses was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients. Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.

Secondary Outcome Measures

Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia).
The proportion of responses in Waldenstrom's macroglobulinemia was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients. Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.
Survival Time
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Progression-free Survival Time
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. Progressive disease is defined as having one of the following: The appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from nadir in the sum of the product of the dimension (SPD) of any previously involved nodes. At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.
Time to Treatment Failure
Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.

Full Information

First Posted
November 1, 2008
Last Updated
August 25, 2016
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00784927
Brief Title
Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone in Treating Patients With Previously Untreated Low-Grade Non-Hodgkin Lymphoma
Official Title
A Phase 2 Study of Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone (LR-CD) for Untreated Low Grade Non-Hodgkin Lymphoma Requiring Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab, cyclophosphamide, and dexamethasone may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving lenalidomide together with rituximab, cyclophosphamide, and dexamethasone works in treating patients with previously untreated low-grade non-Hodgkin lymphoma.
Detailed Description
OBJECTIVES: Primary To assess tumor response to lenalidomide, rituximab, cyclophosphamide, and dexamethasone in patients with symptomatic previously untreated low-grade non-Hodgkin lymphoma. Secondary To describe the adverse event profile of this regimen. To evaluate overall survival, progression-free survival, duration of response, and time to treatment failure associated with this regimen. To estimate tumor response to lenalidomide, rituximab, cyclophosphamide and dexamethasone in the subgroup of patients with lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia). OUTLINE: This is a multicenter study. Patients receive oral lenalidomide once daily on days 1-21, rituximab IV on day 1, oral cyclophosphamide once daily on days 1, 8, and 15, and oral dexamethasone once daily on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 3 months for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
stage I grade 1 follicular lymphoma, contiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, stage III grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage I small lymphocytic lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, Waldenstrom macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, stage I marginal zone lymphoma, contiguous stage II marginal zone lymphoma, noncontiguous stage II marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Primary Outcome Measure Information:
Title
Assessment of Tumor Response
Description
The proportion of responses was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients. Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.
Time Frame
Up to 1 year from registration.
Secondary Outcome Measure Information:
Title
Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia).
Description
The proportion of responses in Waldenstrom's macroglobulinemia was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients. Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.
Time Frame
Up to 1 year from registration.
Title
Survival Time
Description
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time Frame
Up to 1 year from registration.
Title
Progression-free Survival Time
Description
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. Progressive disease is defined as having one of the following: The appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. At least a 50% increase from nadir in the sum of the product of the dimension (SPD) of any previously involved nodes. At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.
Time Frame
Up to 1 year from registration.
Title
Time to Treatment Failure
Description
Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.
Time Frame
Up to 1 year from registration.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed symptomatic non-Hodgkin lymphoma by biopsy within the past 6 months Any of the following subtypes allowed: Grade 1 or 2 lymphoma Small lymphocytic lymphoma Marginal zone lymphoma Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia [WM]) Previously untreated disease that, in the investigator's opinion, requires treatment Measurable disease by CT or MRI scans with lymph nodes ≥ 2.0 cm in ≥ 1 dimension WM patients without lymphadenopathy must meet the following criteria: More than 10% lymphocytes, lymphoplasmacytic cells, or plasma cells on a bone marrow aspirate/biopsy Quantitative Immunoglobulin M ≥ 400 mg/dL NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: ECOG performance status 0-2 ANC ≥ 1,400/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 2.0 mg/dL Total or direct bilirubin ≤ 1.5 mg/dL AST and ALT ≤ 2 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-method contraception at least 28 days prior to, during, and for 28 days after completion of study therapy Able to take acetylsalicylic acid (ASA) 325 mg/day as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin) No known hypersensitivity to thalidomide No development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situations that would limit compliance with study requirements No myocardial infarction within the past 6 months No other active malignancy requiring treatment, except for localized nonmelanomatous skin cancer or any cancer that, in the judgement of the investigator, has been treated with curative intent and will not interfere with the study treatment plan and response assessment No co-morbid systemic illnesses or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or would interfere significantly with the proper assessment of safety and toxicity of study treatment No known positivity for HIV or infectious hepatitis A, B, or C No serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent Willing to return to Mayo Clinic enrolling institution for follow up Registered into the RevAssist® program and willing and able to comply with the requirements of RevAssist® PRIOR CONCURRENT THERAPY: No prior lenalidomide No prior irradiation to ≥ 25% of the bone marrow More than 28 days since prior experimental drug or therapy No concurrent radiotherapy, chemotherapy, or immunotherapy No other concurrent anticancer agents or treatments, including thalidomide or investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig B Reeder, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Thomas E. Witzig, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259-5499
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone in Treating Patients With Previously Untreated Low-Grade Non-Hodgkin Lymphoma

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