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Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non-Hodgkin's Lymphoma

Phase 2
Active, not recruiting
Conditions
Non Hodgkin's Lymphoma
Interventions
Registration Number
NCT01316523
Lead Sponsor
University of California, Davis
Brief Summary

Lenalidomide has been shown to have single agent activity in indolent Non-Hodgkin's Lymphoma. It is approved for the treatment of multiple myeloma and myelodysplastic syndrome.

Rituximab is effective as a single agent and in combination with chemotherapy for indolent Non-Hodgkin's Lymphoma.

The purpose of this study is to see how well giving lenalidomide together with rituximab works in treating patients with previously untreated indolent Non Hodgkin's Lymphoma.

Lenalidomide will taken at 20 mg daily, days 1-21 of a 28 day cycle, to be continued until the disease progresses, unacceptable side effects or after twelve cycles if the patient is responding well.

Rituximab 375 mg/m2/wk x 4 weeks will begin on Day 15 of cycle 1. After 4 cycles of therapy, if patients respond well to treatment, patients will receive a second course of Rituximab.

Blood samples will be collected to assess how the immune system is functioning.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria
  1. All patients must be informed of the investigative nature of the clinical trial and given written informed consent in accordance with institutional and federal guidelines.

  2. Age greater than or equal to 18 years at the time of signing the informed consent form.

  3. Able to adhere to the study visit schedule and other protocol requirements.

  4. Previously untreated, histologically confirmed indolent lymphoma including follicle cell lymphoma, WHO classification, grade I or II, and marginal zone lymphoma. Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies. Fine needle aspirates are not acceptable.

  5. At least one measurable lesion according to the International Working Group Response criteria for lymphomas. There must be measurable lymphadenopathy to follow with serial exam and/or imaging.

  6. Submission of original biopsy for review by local staff hematopathologist.

  7. ECOG performance status of 0 -2 at study entry.

  8. No major organ dysfunction with laboratory test results within these ranges:

    • Absolute neutrophil count greater than or equal to 1000 /uL
    • Platelet count greater than or equal to 75 x 109/L
    • Total bilirubin less than or equal to 2.0 mg/dL.
    • HIV negative
    • Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance ≥ 30ml/min and < 60ml/min.
  9. Life expectancy of greater than 3 months.

  10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

  11. Disease free of prior malignancies for greater than or equal to 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

  12. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients who are intolerant to aspirin may use low molecular weight heparin).

  13. Must be able to swallow lenalidomide capsules.

Exclusion Criteria
  1. Any prior treatment for Non-Hodgkin's Lymphoma.
  2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  3. Pregnant or breast-feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  4. 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.
  5. Use of any other experimental drug or therapy within 28 days of baseline.
  6. Known hypersensitivity to thalidomide or rituximab.
  7. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  8. Any prior use of lenalidomide.
  9. Concurrent use of other anti-cancer agents or treatments.
  10. Known positive for HIV
  11. Known active hepatitis, type A, B or C.
  12. Evidence for CNS metastatic disease
  13. Subjects with ≥ Grade 2 neuropathy

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lenalidomide + RituximabRituximabPatients will receive lenalidomide 20 mg daily (oral), on days 1-21 of a 28 day cycle. Rituximab 375 mg/m2 (into the vein) will be administered weekly for 4 doses starting day 15 of cycle 1, to be repeated if patient does not achieve a complete response after cycle 4, on days 1, 8, 15 and 22 of cycle 5.
Lenalidomide + RituximabLenalidomidePatients will receive lenalidomide 20 mg daily (oral), on days 1-21 of a 28 day cycle. Rituximab 375 mg/m2 (into the vein) will be administered weekly for 4 doses starting day 15 of cycle 1, to be repeated if patient does not achieve a complete response after cycle 4, on days 1, 8, 15 and 22 of cycle 5.
Primary Outcome Measures
NameTimeMethod
Response rate to treatment4 months

Responses will be assessed by the Revised Working Group Response Criteria for Malignant Lymphoma. A complete response is the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is regression of measurable disease and no new sites of disease. Stable disease is failure to attain a complete response/partial response or progressive disease.

Secondary Outcome Measures
NameTimeMethod
Time to progressionUp to two years.

Time to progression will be measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression, or the date of death if the patient dies due to causes other than disease progression

Overall survivalUp to two years.

Overall survival wil be measured as the time from start of treatment to the date of death or the last date the patient was known to be alive

Tolerability defined by frequency, severity and relationship of adverse events to study treatmentUp to two years.

Tolerability means the type, frequency, severity and relationship of adverse events to study treatment based on the National Cancer Institute Common Toxicity Criteria Version 4.0

Duration of response from start of therapyUp to two years.

The duration of response is measured from the time measurement criteria are met for complete response/partial response(whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

The duration of response is measured from the time measurement criteria are first met for complete response until the first date that recurrent disease is objectively documented.

Trial Locations

Locations (2)

University of California Davis Cancer Center

🇺🇸

Sacramento, California, United States

Sutter Pacific Medical Foundation

🇺🇸

Santa Rosa, California, United States

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