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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00784927
First received: November 1, 2008
Last updated: April 18, 2016
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: dexamethasone
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone (LR-CD) for Untreated Low Grade Non-Hodgkin Lymphoma Requiring Therapy

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Assessment of Tumor Response [ Time Frame: Up to 1 year from registration. ] [ Designated as safety issue: No ]

    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). [ Time Frame: Up to 1 year from registration. ] [ Designated as safety issue: No ]

    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 [ Time Frame: Up to 1 year from registration. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 1 year from registration. ] [ Designated as safety issue: No ]

    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 Frame: Up to 1 year from registration. ] [ Designated as safety issue: No ]
    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.


Enrollment: 36
Study Start Date: November 2008
Study Completion Date: August 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

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.

Biological: rituximab Drug: cyclophosphamide Drug: dexamethasone Drug: lenalidomide

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.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00784927

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Study Chair: Craig B Reeder, MD Mayo Clinic
Principal Investigator: Thomas E. Witzig, MD Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00784927     History of Changes
Other Study ID Numbers: MC0882  P30CA015083  MC0882  RV-NHL-PI-0336  08-001485 
Study First Received: November 1, 2008
Results First Received: March 23, 2015
Last Updated: April 18, 2016
Health Authority: United States: Federal Government

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Cyclophosphamide
Rituximab
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016