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

Primary Purpose

Non Hodgkin's Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Lenalidomide
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non Hodgkin's Lymphoma focused on measuring Lenalidomide, Rituximab, untreated indolent Non-Hodgkin's Lymphoma

Eligibility Criteria

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

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

Sites / Locations

  • University of California Davis Cancer Center
  • Sutter Pacific Medical Foundation

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide + Rituximab

Arm Description

Patients 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.

Outcomes

Primary Outcome Measures

Response rate to treatment
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

Time to progression
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 survival
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 treatment
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 therapy
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.

Full Information

First Posted
February 4, 2011
Last Updated
August 30, 2023
Sponsor
University of California, Davis
Collaborators
Celgene
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1. Study Identification

Unique Protocol Identification Number
NCT01316523
Brief Title
Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non-Hodgkin's Lymphoma
Official Title
Phase II Study of Lenalidomide and Rituximab in Subjects With Previously Untreated Indolent Non Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 2010 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Davis
Collaborators
Celgene

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hodgkin's Lymphoma
Keywords
Lenalidomide, Rituximab, untreated indolent Non-Hodgkin's 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
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide + Rituximab
Arm Type
Experimental
Arm Description
Patients 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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab 375 mg/m2/wk x 4 weeks, to begin Day 15 of cycle 1. After 4 cycles of therapy if patient does not respond to treatment, the patient will receive a second course of Rituximab.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Lenalidomide will be taken at 20 mg daily, days 1-21 of a 28 day cycle, to be continued until the disease progresses, there are too many side effects, or after twelve cycles if the patient responds to treatment.
Primary Outcome Measure Information:
Title
Response rate to treatment
Description
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.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Time to progression
Description
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
Time Frame
Up to two years.
Title
Overall survival
Description
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
Time Frame
Up to two years.
Title
Tolerability defined by frequency, severity and relationship of adverse events to study treatment
Description
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
Time Frame
Up to two years.
Title
Duration of response from start of therapy
Description
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.
Time Frame
Up to two years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Age greater than or equal to 18 years at the time of signing the informed consent form. Able to adhere to the study visit schedule and other protocol requirements. 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. 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. Submission of original biopsy for review by local staff hematopathologist. ECOG performance status of 0 -2 at study entry. 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. Life expectancy of greater than 3 months. 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. 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 Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients who are intolerant to aspirin may use low molecular weight heparin). Must be able to swallow lenalidomide capsules. Exclusion Criteria: Any prior treatment for Non-Hodgkin's Lymphoma. 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 rituximab. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. Any prior use of lenalidomide. Concurrent use of other anti-cancer agents or treatments. Known positive for HIV Known active hepatitis, type A, B or C. Evidence for CNS metastatic disease Subjects with ≥ Grade 2 neuropathy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph Tuscano, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Sutter Pacific Medical Foundation
City
Santa Rosa
State/Province
California
ZIP/Postal Code
95403
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24606326
Citation
Tuscano JM, Dutia M, Chee K, Brunson A, Reed-Pease C, Abedi M, Welborn J, O'Donnell RT. Lenalidomide plus rituximab can produce durable clinical responses in patients with relapsed or refractory, indolent non-Hodgkin lymphoma. Br J Haematol. 2014 May;165(3):375-81. doi: 10.1111/bjh.12755. Epub 2014 Mar 7.
Results Reference
derived

Learn more about this trial

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

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