Rituximab, Fludarabine, Mitoxantrone, Dexamethasone (R-FND) Plus Zevalin for High-Risk Follicular Lymphoma

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00290511
Collaborator
Genentech, Inc. (Industry), Biogen (Industry)
49
1
1
199.5
0.2

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if chemotherapy given with rituximab, followed by Ibritumomab tiuxetan (Zevalin), and then followed by rituximab can help to control lymphoma. The safety of this treatment schedule will also be studied.

Objectives:
  1. To assess whether the time to progression for these high-risk patients can be prolonged to a median of 36 months, compared to the historical expectation of approximately 24 months.

  2. To assess the tolerance and efficacy of Y2B8 (Zevalin) after R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) in patients with high-risk stage III-IV follicular lymphoma

  3. To assess overall response, failure-free survival, and survival of this strategy compared to our historical experience with FND (fludarabine, mitoxantrone, dexamethasone) alone or R-FND

  4. To assess the tolerance and efficacy of maintenance therapy with rituximab.

  5. To maximize the 12-month molecular remission rate for patients with high-risk stage III-IV follicular lymphoma

  6. to correlate the results of quantitative PCR assay with classical PCR and with clinical outcome

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The treatments used in this program include several standard chemotherapy agents (fludarabine, mitoxantrone, and dexamethasone). Also, immune therapy agents will be given, including rituximab (a monoclonal antibody that attacks B-cells, which is what this type of lymphoma is made of), and Ibritumomab tiuxetan (another similar monoclonal antibody, which delivers radiation to the lymphoma cells to strengthen the attack).

You will receive rituximab on Days 1 and 8 of the first cycle, and on Day 1 only of Cycles 2-4 of the monthly cycles of chemotherapy, called R-FND. R-FND includes rituximab and fludarabine, mitoxantrone, and dexamethasone. Fludarabine will be given for 3 days, mitoxantrone for 1 day, and dexamethasone for 5 days of each 28-day cycle (FND). After 4 cycles of R-FND, you will receive Ibritumomab tiuxetan. After the Ibritumomab tiuxetan, you will receive rituximab every 2 months for 1 year. All are given by vein. Sometimes dexamethasone can be given in pill form.

During the study, you will have blood tests (about 2 tablespoons), sometimes every week. Every 2 cycles, you will have a chest x-ray and CT scans of the abdomen and pelvis. Bone marrow samples will be taken. Heart function tests will be done as needed.

If you desire, it may be possible for you to receive some of your study treatment at home (from your home doctor). Your study doctor will discuss this possibility with you. If this is the case, your home doctor will receive a letter telling him about this study and asking him if he wishes to participate in your treatments. He will be asked to provide the study doctors at M. D. Anderson specific information about your treatments and any side effects you may have. All communications between your home doctor and your study doctors will be included as part of your M. D. Anderson medical record.

After the study ends, you will return for checkups every 3 months in the first year, every 4 months in Years 2 and 3, and every 6 months in Years 4 and 5. After that, checkups will be needed once a year. Blood (about 2 tablespoons) and bone marrow samples will be taken at these visits.

This is an investigational study. Ibritumomab tiuxetan and rituximab are approved by the FDA for commercial use. The other drugs used in the study are also approved for commercial use by the FDA. About 50 patients will take part in the study. All will be enrolled at M. D. Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of R-FND, Followed by Zevalin Radioimmunotherapy, and Subsequent Maintenance Rituximab for Advanced Stage Follicular Lymphoma With High-Risk Features
Actual Study Start Date :
Jun 29, 2004
Actual Primary Completion Date :
Feb 12, 2021
Actual Study Completion Date :
Feb 12, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: R-FIND + Zevalin

Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.

Drug: Fludarabine
25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4.
Other Names:
  • Fludarabine Phosphate
  • Fludara
  • Drug: Mitoxantrone
    10 mg/m^2 IV over 5-30 minutes on Day 2.
    Other Names:
  • Novantrone
  • Drug: Rituximab
    375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total).
    Other Names:
  • Rituxan
  • Drug: Zevalin
    0.3 mCi/kg IV after 4 cycles of R-FND.
    Other Names:
  • Ibritumomab Tiuxetan
  • IDEC-Y2B8
  • Drug: Dexamethasone
    20 mg by mouth (PO) or IV daily on Days 2-6.
    Other Names:
  • Decadron
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Time to Progression (TTP) [baseline, 2 and 4 courses, approximately month 8, 9, and 12 months, then restaging every 4 months, then at 2 years every 4-6 months, then yearly until progressive disease or lost to follow up, average of 10 years]

      Regimen regarded as a success if median TTP can be prolonged to 36 months or greater. Time to Progression measured by the method of Kaplan and Meier, and accompanied by 95% confidence interval. Complete Response (CR) defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays and Partial Response (PR) is defined as a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. av

    Secondary Outcome Measures

    1. Tolerance and Efficacy of Maintenance Therapy With Yttrium-90 Ibritumomab Tiuxetan (YIT) [cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years]

      To assess the tolerance and efficacy of maintenance therapy with YIT. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.

    2. Tolerance and Efficacy of Maintenance Therapy With Rituximab [cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years]

      To assess the tolerance and efficacy of maintenance therapy with rituximab. Participants proceeded to the rituximab maintenance program of 6 treatments comprising 1 every 2 months. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.

    3. Median Progression Free Survival [up to 5 years]

      Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. Median Progression Free Survival estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    4. Progression Free Survival at 10 Years [10 years]

      Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. PFS was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    5. Overall Survival [up to 5 years]

      OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Median Overall Survival was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    6. Percentage of Participants With Overall Survival Rate at 10 Years [10 years]

      OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Overall Survival Rate estimated by the method of Kaplan and Meier.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients with high-risk Ann Arbor stage III-IV follicular lymphoma. High-risk is defined by advanced stage (III or IV), plus any 2 of the following features: age 60 or greater; elevated LDH; Hgb < 12; or number of involved nodal sites 5 or more .

    2. Patients will be previously untreated.

    3. Adequate organ function.

    4. Follicular lymphoma, grade 3 (follicular large cell lymphoma): If eligible for a current large cell lymphoma protocol, that alternative protocol is recommended, particularly grade 3b or FLCL patients characterized as large non-cleaved cell. However, both FND and rituximab have established efficacy in FLCL, so if a patient is not eligible for a protocol for aggressive lymphoma (e.g., because of SCCL in the marrow), then registration on this trial is permitted.

    5. Biopsy or fine-needle aspiration (FNA) material is strongly recommended for bcl-2 studies to verify rearrangement status of all patients who are designated "germline". (see section 6.4). For other patients, tissue availability is desirable but not mandatory.

    6. Patients must have a performance status of Zubrod 3 or better

    7. Patients must have adequate renal and hepatic function (creatinine < 2mg%; bilirubin < 2 mg%). Patients with renal or liver dysfunction due to organ infiltration by lymphoma may be eligible after discussion with the study chairman.

    8. Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy.

    9. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.

    Exclusion Criteria:
    1. Patients who are unable or unlikely to be able to adhere to the treatment plan or to return to Houston for follow-up visits because of geographical, economic, emotional, or social considerations are not eligible for this study. Note: some follow-up care may be provided by outside physicians as long as the MD Anderson Cancer Center (MDACC) protocol for outside physician participation is strictly adhered to.

    2. Patients with an absolute peripheral granulocyte count of < 1,000 and platelet count < 100,000 unless due to marrow infiltration or hypersplenism.

    3. Patients with organ dysfunction, including bilirubin of > 2 mg% or serum creatinine level > 2 mg%, unless the alteration is due to lymphoma.

    4. Patients with HIV infection should not be registered on this protocol.

    5. Patients with an antecedent malignancy whose prognosis is poor (< 90% probability of surviving for 5 yrs).

    6. All patients should have a cardiac ejection fraction of 50% or more by echocardiography or multiple gated acquisition scan (MUGA).

    7. Patients who will not accept transfusions of blood products or supportive care measures such as antibiotics are not eligible for this study.

    8. Female patients must not be pregnant or lactating, and men and women of reproductive potential must follow accepted birth control methods.

    9. Patients who have received prior murine antibody therapy will be excluded.

    10. Patients with evidence of active or prior infection of Hepatitis B are excluded. (Note: Persons vaccinated for Hepatitis B who have + antibodies are not excluded).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Texas MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • Genentech, Inc.
    • Biogen

    Investigators

    • Principal Investigator: Nathan Fowler, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00290511
    Other Study ID Numbers:
    • ID03-0287
    • NCI-2011-02453
    First Posted:
    Feb 13, 2006
    Last Update Posted:
    Apr 22, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by M.D. Anderson Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Recruitment period from June 2004 to May 2009.
    Pre-assignment Detail Forty-nine patients with Follicular Lymphoma were enrolled in this single site, phase II trial. Two patients were removed after registration and did not start treatment: the first, due to physician's decision; the second, to pursue treatment at home.
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Period Title: Overall Study
    STARTED 49
    No Treatment Per Protocol 2
    Toxicity Assessment 47
    Response Assessment 45
    COMPLETED 45
    NOT COMPLETED 4

    Baseline Characteristics

    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Overall Participants 49
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    29
    59.2%
    >=65 years
    20
    40.8%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    62
    Sex: Female, Male (Count of Participants)
    Female
    25
    51%
    Male
    24
    49%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    2%
    Not Hispanic or Latino
    25
    51%
    Unknown or Not Reported
    23
    46.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    3
    6.1%
    White
    43
    87.8%
    More than one race
    0
    0%
    Unknown or Not Reported
    2
    4.1%
    Region of Enrollment (participants) [Number]
    United States
    49
    100%
    Bulky Disease (Count of Participants)
    Bulky Disease >/=5 cm
    24
    49%
    No bulky disease
    25
    51%
    Ann Arbor Stages (Count of Participants)
    Ann Arbor Stage III
    7
    14.3%
    Ann Arbor Stage IV
    42
    85.7%
    Follicular Lymphoma International Prognostic Index (FLIPI) (Count of Participants)
    FLIPI Score 3
    40
    81.6%
    FLIPI Score 4
    6
    12.2%
    FLIPI Score 5
    2
    4.1%
    Bone Marrow Biopsy (Count of Participants)
    Bone Marrow Biopsy - Neg
    11
    22.4%
    Bone Marrow Biopsy - Pos
    37
    75.5%
    Lactate Dehydrogenase (LDH) (Count of Participants)
    LDH, units/ </= 618
    35
    71.4%
    LDH, units/ >618
    14
    28.6%
    Beta 2 Microglobulin (B2M) (Count of Participants)
    B2M, mg/l <2.2
    15
    30.6%
    B2M, mg/l>/= 2.2
    33
    67.3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Time to Progression (TTP)
    Description Regimen regarded as a success if median TTP can be prolonged to 36 months or greater. Time to Progression measured by the method of Kaplan and Meier, and accompanied by 95% confidence interval. Complete Response (CR) defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays and Partial Response (PR) is defined as a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. av
    Time Frame baseline, 2 and 4 courses, approximately month 8, 9, and 12 months, then restaging every 4 months, then at 2 years every 4-6 months, then yearly until progressive disease or lost to follow up, average of 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 49
    Complete Response (CR)
    42
    85.7%
    Partial Response (PR)
    4
    8.2%
    2. Secondary Outcome
    Title Tolerance and Efficacy of Maintenance Therapy With Yttrium-90 Ibritumomab Tiuxetan (YIT)
    Description To assess the tolerance and efficacy of maintenance therapy with YIT. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.
    Time Frame cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years

    Outcome Measure Data

    Analysis Population Description
    Participants that received YIT treatment.
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 38
    Complete Response (CR)
    37
    75.5%
    Progressive Disease
    1
    2%
    3. Secondary Outcome
    Title Tolerance and Efficacy of Maintenance Therapy With Rituximab
    Description To assess the tolerance and efficacy of maintenance therapy with rituximab. Participants proceeded to the rituximab maintenance program of 6 treatments comprising 1 every 2 months. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.
    Time Frame cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 41
    Complete Response (CR)
    38
    77.6%
    Progression Disease (PD)
    3
    6.1%
    4. Secondary Outcome
    Title Median Progression Free Survival
    Description Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. Median Progression Free Survival estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.
    Time Frame up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 47
    Median (95% Confidence Interval) [months]
    84
    5. Secondary Outcome
    Title Progression Free Survival at 10 Years
    Description Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. PFS was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.
    Time Frame 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 47
    Number (95% Confidence Interval) [months]
    49
    6. Secondary Outcome
    Title Overall Survival
    Description OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Median Overall Survival was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.
    Time Frame up to 5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 47
    Number (95% Confidence Interval) [months]
    143
    7. Secondary Outcome
    Title Percentage of Participants With Overall Survival Rate at 10 Years
    Description OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Overall Survival Rate estimated by the method of Kaplan and Meier.
    Time Frame 10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    Measure Participants 47
    Number [percentage of participants]
    69
    140.8%

    Adverse Events

    Time Frame Adverse event reporting per patient done beginning at the start intervention per protocol through 30 days post intervention completion, up to 10 years
    Adverse Event Reporting Description
    Arm/Group Title R-FIND + Zevalin
    Arm/Group Description Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
    All Cause Mortality
    R-FIND + Zevalin
    Affected / at Risk (%) # Events
    Total 8/49 (16.3%)
    Serious Adverse Events
    R-FIND + Zevalin
    Affected / at Risk (%) # Events
    Total 34/49 (69.4%)
    Blood and lymphatic system disorders
    Neutropenia 21/49 (42.9%)
    Thrombocytopenia 16/49 (32.7%)
    Anemia 1/49 (2%)
    Cardiac disorders
    Dyspnea 5/49 (10.2%)
    Syncope 1/49 (2%)
    Eye disorders
    Blurred Vision 3/49 (6.1%)
    Gastrointestinal disorders
    Constipation 2/49 (4.1%)
    Diarrhea 1/49 (2%)
    General disorders
    Neutropenic Fever 2/49 (4.1%)
    Secondary Malignancy 2/49 (4.1%)
    Fatigue 8/49 (16.3%)
    Pain 6/49 (12.2%)
    Chest pain, non-cardiac 2/49 (4.1%)
    Edema, face 2/49 (4.1%)
    Rigors/chills 1/49 (2%)
    Immune system disorders
    Allergic reaction 2/49 (4.1%)
    Flushing 1/49 (2%)
    Infections and infestations
    Infection, normal ANC 3/49 (6.1%)
    Nervous system disorders
    Dizziness 3/49 (6.1%)
    Peripheral sensory neuropathy 1/49 (2%)
    Other (Not Including Serious) Adverse Events
    R-FIND + Zevalin
    Affected / at Risk (%) # Events
    Total 46/49 (93.9%)
    Blood and lymphatic system disorders
    epistaxis 1/49 (2%)
    leukocytosis 3/49 (6.1%)
    lymphocyte count decrease 1/49 (2%)
    neutrophil count decreased 5/49 (10.2%)
    platelet count decreased 1/49 (2%)
    Cardiac disorders
    dyspnea 9/49 (18.4%)
    hiccups 2/49 (4.1%)
    hypotension 2/49 (4.1%)
    Eye disorders
    Blurred Vision 14/49 (28.6%)
    ear and labyrinth disorders - other 1/49 (2%)
    eye disorders- other 11/49 (22.4%)
    watering eyes 11/49 (22.4%)
    Gastrointestinal disorders
    Abdonimal distension 1/49 (2%)
    constipation 22/49 (44.9%)
    diarrhea 18/49 (36.7%)
    flatulence 1/49 (2%)
    gastritis 2/49 (4.1%)
    GI disorders- other 1/49 (2%)
    musositis oral 11/49 (22.4%)
    muculoskeletal and connective tissue disorder - other 1/49 (2%)
    nausea 23/49 (46.9%)
    obstruction gastric 1/49 (2%)
    rectal pain 1/49 (2%)
    vomiting 6/49 (12.2%)
    General disorders
    chills 10/49 (20.4%)
    Edema, face 4/49 (8.2%)
    edema, limbs 8/49 (16.3%)
    fatigue 18/49 (36.7%)
    fever 11/49 (22.4%)
    flu like symptoms 1/49 (2%)
    insomnia 3/49 (6.1%)
    non-cardiac chest pain 3/49 (6.1%)
    pain 8/49 (16.3%)
    pain in extremity 3/49 (6.1%)
    Immune system disorders
    Allergic reaction 5/49 (10.2%)
    Allergic rhinitis 1/49 (2%)
    Infections and infestations
    Bronchial infection 2/49 (4.1%)
    infections other 7/49 (14.3%)
    lip infection 1/49 (2%)
    lung infection 1/49 (2%)
    mucosal infection 1/49 (2%)
    urinary tract infection 1/49 (2%)
    Investigations
    Bilirubin increased 1/49 (2%)
    creatinine increased 2/49 (4.1%)
    Metabolism and nutrition disorders
    ALT increased 1/49 (2%)
    AST increased 1/49 (2%)
    hyperglycemia 1/49 (2%)
    hyperuricemia 1/49 (2%)
    hypokalemia 1/49 (2%)
    Musculoskeletal and connective tissue disorders
    Back pain 3/49 (6.1%)
    flank pain 1/49 (2%)
    generalized muscle weakness 1/49 (2%)
    kyphosis 1/49 (2%)
    myalgia 4/49 (8.2%)
    peripheral motor neuropathy 1/49 (2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    neoplasms 1/49 (2%)
    Nervous system disorders
    dizziness 18/49 (36.7%)
    headache 7/49 (14.3%)
    memory impairment 10/49 (20.4%)
    nervous systems disorders - other 1/49 (2%)
    peripheral sensory neuropathy 8/49 (16.3%)
    somnolence 1/49 (2%)
    tremor 1/49 (2%)
    Renal and urinary disorders
    urinary frequency 1/49 (2%)
    urinary tract pain 1/49 (2%)
    Reproductive system and breast disorders
    irregular menstruation 1/49 (2%)
    Respiratory, thoracic and mediastinal disorders
    cough 6/49 (12.2%)
    sinus disorder 1/49 (2%)
    sore throat 2/49 (4.1%)
    Skin and subcutaneous tissue disorders
    Bruising 1/49 (2%)
    dry skin 1/49 (2%)
    flushing 1/49 (2%)
    pruritus 3/49 (6.1%)
    rash maculo-papular 7/49 (14.3%)
    skin disorders - other 2/49 (4.1%)
    skin hyperpigmentation 1/49 (2%)
    skin infection 1/49 (2%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Felipe Samaniego, MD-Professor, Lymphoma-Myeloma
    Organization UT MD Anderson Cancer Center
    Phone (713) 745-6824
    Email fsamaniego@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00290511
    Other Study ID Numbers:
    • ID03-0287
    • NCI-2011-02453
    First Posted:
    Feb 13, 2006
    Last Update Posted:
    Apr 22, 2022
    Last Verified:
    Mar 1, 2022