Fludarabine, Bendamustine, and Rituximab (FBR) for Relapsed Chronic Lymphocytic Leukemia (CLL)

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01096992
Collaborator
(none)
51
Enrollment
1
Location
5
Arms
83.4
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of bendamustine, combined with fludarabine and rituximab, that can be given to patients who have CLL that has been treated before.

The goal of Phase 2 of this study is to find out if this drug combination can help to control the disease. The safety of this drug combination will also be studied.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Detailed Description

The Study Drugs:

Fludarabine and bendamustine are designed to damage the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.

Rituximab is designed to attach to cancer cells and damage them, which may cause the cancer cells to die. It is also designed to cause the immune system to attack cancer cells.

Study Drug Dose Levels:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. One (1) to 8 groups with 3-6 participants will be enrolled in the Phase 1 portion of the study, and up to 58 participants will be enrolled in Phase 2.

If you are enrolled in Phase 1, the dose of bendamustine you receive will depend on when you joined this study. The first group will receive the lowest dose. The next group will receive a higher dose, if the number and type of side effects was low or none. The dose of bendamustine will be increased for each new group until the highest tolerable dose is found.

If you are enrolled in Phase 2, you will receive bendamustine at the highest dose that was tolerated in Phase 1.

All participants in both phases of the study will start out with the same dose levels of fludarabine and rituximab.

If side effects occur, the study doctor may decide to lower your doses of study therapy. If you have side effects during a dose, the study staff will observe you for any other problems for 2 hours after the dose.

Study Drug Administration:

Cycles in this study are 4 weeks. All 3 study drugs are given by vein.

Cycle 1:
  • On Days 1-3, bendamustine will be given over 30 minutes.

  • On Days 2-4, fludarabine will be given over 30 minutes.

  • On Day 4, rituximab will be given over 6-8 hours.

Cycles 2-6:
  • On Day 1, rituximab will be given at a higher dose than in Cycle 1. If you tolerated the Cycle 1 dose well, your Cycles 2-6 rituximab doses may be given over 2-4 hours.

  • On Days 1-3, fludarabine will be given over 30 minutes.

  • On Days 1-3, bendamustine will be given over 30 minutes.

Other Drugs:

You will be given Tylenol (acetaminophen) and Benadryl (diphenhydramine hydrochloride) to take by mouth 30-60 minutes before every dose of rituximab (Cycles 1-6). These drugs are given to lower the risk of side effects.

Study Visits:

Once a week in Cycle 1 and every 2-4 weeks in Cycles 2-6, blood (about 1 tablespoon) will be drawn for routine tests.

Before Cycles 1-6, you will also have a physical exam, including measurement of your vital signs. You will be asked about any side effects you may have had.

Before Cycle 4, the following tests and procedures will be performed:
  • You will have a physical exam.

  • Blood (about 2 tablespoons) will be drawn for routine tests.

  • You will have a bone marrow aspiration and biopsy to check the status of the disease.

  • If the doctor thinks it is needed, you will have a CT scan of the neck, chest, abdomen, and pelvis to check the status of the disease.

Length of Study Participation:

You may receive up to 6 cycles of study treatment. The study treatment will be stopped early if the disease gets worse or you experience any intolerable side effects.

End-of-Treatment Visit:

After Cycle 6 (or earlier if you stop early), the following tests and procedures will be performed:

  • You will have a physical exam.

  • Blood (about 2 tablespoons) will be drawn for routine tests.

  • You will have a bone marrow aspiration and biopsy to check the status of the disease.

  • If the doctor thinks the disease has completely responded, you will have a CT scan of the neck, chest, abdomen, and pelvis to confirm the response.

Follow-Up Visits:

You will have follow-up visits at the end of Month 6 and Year 1 after your last dose of study drugs, and once a year until you start a new cancer treatment. The same tests will be performed as at the end-of-treatment visit. Starting at Year 3, the follow-up tests and procedures can be done by your local doctor if that is more convenient to you.

You should tell your study doctor or staff if you start another cancer treatment after the study. If that occurs, your follow-up in this study will stop.

This is an investigational study. Both fludarabine and bendamustine are commercially available and FDA approved to treat CLL. Rituximab is commercially available and FDA approved to treat lymphoma. The use of these drugs together in this study is investigational.

Up to 82 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
51 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Clinical Trial of Fludarabine, Bendamustine, and Rituximab (FBR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Apr 19, 2010
Actual Primary Completion Date :
Mar 31, 2017
Actual Study Completion Date :
Mar 31, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Phase 1 20 mg/m^2

Bendamustine, Fludarabine + Rituximab

Drug: Bendamustine
Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine)
Other Names:
  • Bendamustine HCI
  • Bendamustine Hydrochloride
  • CEP-18083
  • SDX-105
  • Treanda
  • Drug: Fludarabine
    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3
    Other Names:
  • Fludara
  • Fludarabine Phosphate
  • Drug: Rituximab
    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Other Names:
  • Rituxan
  • Experimental: Phase 2

    Bendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab

    Drug: Bendamustine
    Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine)
    Other Names:
  • Bendamustine HCI
  • Bendamustine Hydrochloride
  • CEP-18083
  • SDX-105
  • Treanda
  • Drug: Fludarabine
    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3
    Other Names:
  • Fludara
  • Fludarabine Phosphate
  • Drug: Rituximab
    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Other Names:
  • Rituxan
  • Experimental: Phase 1 30 mg/m^2

    Bendamustine, Fludarabine + Rituximab

    Drug: Bendamustine
    Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine)
    Other Names:
  • Bendamustine HCI
  • Bendamustine Hydrochloride
  • CEP-18083
  • SDX-105
  • Treanda
  • Drug: Fludarabine
    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3
    Other Names:
  • Fludara
  • Fludarabine Phosphate
  • Drug: Rituximab
    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Other Names:
  • Rituxan
  • Experimental: Phase 1 40 mg/m^2

    Bendamustine, Fludarabine + Rituximab

    Drug: Bendamustine
    Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine)
    Other Names:
  • Bendamustine HCI
  • Bendamustine Hydrochloride
  • CEP-18083
  • SDX-105
  • Treanda
  • Drug: Fludarabine
    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3
    Other Names:
  • Fludara
  • Fludarabine Phosphate
  • Drug: Rituximab
    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Other Names:
  • Rituxan
  • Experimental: Phase 1 50 mg/m^2

    Bendamustine, Fludarabine + Rituximab

    Drug: Bendamustine
    Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine)
    Other Names:
  • Bendamustine HCI
  • Bendamustine Hydrochloride
  • CEP-18083
  • SDX-105
  • Treanda
  • Drug: Fludarabine
    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3
    Other Names:
  • Fludara
  • Fludarabine Phosphate
  • Drug: Rituximab
    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Other Names:
  • Rituxan
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR) [After 4 week cycle]

      MTD defined as highest dose level in which 6 participants have been treated with </= to 1 patient experiencing dose limiting toxicity (DLT). MTD exceeded if 2 or more of 6 patients experience grade 3 or higher, non-hematologic, non-infusion related toxicity a major organ system. DLT defined as treatment-related, grade >/= 3 non-hematologic toxicity. Hematologic toxicity grade >/= 3 that lasts longer than 42 days considered a DLT. Hematologic toxicity graded according to the 2008 IWCLL criteria for grading. Tumor lysis not considered a DLT.

    Secondary Outcome Measures

    1. Overall Response Rate of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR) [Overall response assessed 2 months after 6th or last course if participants not able to receive all 6 intended courses of treatment.]

      Overall Response is Complete response (CR) + Partial response (PR). Overall response evaluated by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 for complete or partial response and progressive disease. Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; positive or negative minimal residual disease (MRD); Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts;

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients must have a diagnosis of CLL/Small Lymphocytic Lymphoma (SLL) and be previously treated

    2. Patients must have an indication for treatment by 2008 IWCLL Criteria

    3. Age >/= 16 years

    4. Zubrod performance status </= 2

    5. Adequate renal and hepatic function as indicated by all the following: a. serum creatinine </= 2 mg/dL AND; b. alanine aminotransferase (ALT) </= 2.5 times upper limit of normal AND; c. total bilirubin </= 2.5 times upper limit of normal

    6. Patients must give written informed consent

    7. Patients of childbearing potential must be willing to practice birth control during the study

    Exclusion Criteria:
    1. Pregnant or breast-feeding females

    2. Significant co-morbidity indicated by major organ system dysfunction

    3. Active, uncontrolled infection, including active hepatitis

    4. Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia purpura (ITP)

    5. Treatment including chemotherapy, chemoimmunotherapy, monoclonal antibody therapy, radiotherapy, high-dose corticosteroid therapy (Prednisone >/ 60 mg daily or equivalent), or immunotherapy within 21 days prior to enrollment or concurrent with this trial

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center

    Investigators

    • Study Chair: William G. Wierda, MD, PhD, BS, 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:
    NCT01096992
    Other Study ID Numbers:
    • 2009-0546
    • NCI-2011-01942
    First Posted:
    Mar 31, 2010
    Last Update Posted:
    Sep 25, 2019
    Last Verified:
    Sep 1, 2019
    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 DetailsRecruitment Period: 4/2010 to 012/2013
    Pre-assignment Detail
    Arm/Group TitlePhase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Arm/Group DescriptionBendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 20 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 30 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 40 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 50 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab Phase 2: 30 mg/m^2 by vein (fixed) on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1
    Period Title: Overall Study
    STARTED636630
    COMPLETED636630
    NOT COMPLETED00000

    Baseline Characteristics

    Arm/Group TitlePhase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2Total
    Arm/Group DescriptionBendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 20 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 30 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 40 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 50 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab Phase 2: 30 mg/m^2 by vein (fixed) on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Total of all reporting groups
    Overall Participants63663051
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    4
    66.7%
    2
    66.7%
    4
    66.7%
    4
    66.7%
    21
    70%
    35
    68.6%
    >=65 years
    2
    33.3%
    1
    33.3%
    2
    33.3%
    2
    33.3%
    9
    30%
    16
    31.4%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    63
    64
    63
    62
    61
    62
    Sex: Female, Male (Count of Participants)
    Female
    2
    33.3%
    2
    66.7%
    1
    16.7%
    0
    0%
    8
    26.7%
    13
    25.5%
    Male
    4
    66.7%
    1
    33.3%
    5
    83.3%
    6
    100%
    22
    73.3%
    38
    74.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    16.7%
    0
    0%
    0
    0%
    1
    16.7%
    2
    6.7%
    4
    7.8%
    White
    5
    83.3%
    3
    100%
    6
    100%
    5
    83.3%
    27
    90%
    46
    90.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    3.3%
    1
    2%
    Region of Enrollment (Count of Participants)
    United States
    6
    100%
    3
    100%
    6
    100%
    6
    100%
    30
    100%
    51
    100%

    Outcome Measures

    1. Primary Outcome
    TitleMaximum Tolerated Dose (MTD) of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR)
    DescriptionMTD defined as highest dose level in which 6 participants have been treated with </= to 1 patient experiencing dose limiting toxicity (DLT). MTD exceeded if 2 or more of 6 patients experience grade 3 or higher, non-hematologic, non-infusion related toxicity a major organ system. DLT defined as treatment-related, grade >/= 3 non-hematologic toxicity. Hematologic toxicity grade >/= 3 that lasts longer than 42 days considered a DLT. Hematologic toxicity graded according to the 2008 IWCLL criteria for grading. Tumor lysis not considered a DLT.
    Time FrameAfter 4 week cycle

    Outcome Measure Data

    Analysis Population Description
    Maximum Tolerated Dose (MTD) was not established as an objective for the phase II portion of this study and was not collected.
    Arm/Group TitlePhase 1
    Arm/Group DescriptionBendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: Starting Dose of 20 mg/m2 IV on Days 1,2,3 (after fludarabine) Phase 2: 30 mg/m2 by vein (fixed) on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1
    Measure Participants21
    Number [mg/m^2]
    30
    2. Secondary Outcome
    TitleOverall Response Rate of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR)
    DescriptionOverall Response is Complete response (CR) + Partial response (PR). Overall response evaluated by 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 for complete or partial response and progressive disease. Complete remission (CR), requiring absence of peripheral blood clonal lymphocytes by immunophenotyping, absence of lymphadenopathy, absence of hepatomegaly or splenomegaly, absence of constitutional symptoms and satisfactory blood counts; positive or negative minimal residual disease (MRD); Partial remission (PR), defined as ≥ 50% fall in lymphocyte count, ≥ 50% reduction in lymphadenopathy or ≥ 50% reduction in liver or spleen, together with improvement in peripheral blood counts;
    Time FrameOverall response assessed 2 months after 6th or last course if participants not able to receive all 6 intended courses of treatment.

    Outcome Measure Data

    Analysis Population Description
    Two participants in the phase II portion of the study were not evaluable for response due to loss to follow-up.
    Arm/Group TitlePhase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Arm/Group DescriptionBendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 20 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 30 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 40 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 50 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab Phase 2: 30 mg/m^2 by vein (fixed) on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1
    Measure Participants636628
    Count of Participants [Participants]
    5
    83.3%
    3
    100%
    5
    83.3%
    2
    33.3%
    17
    56.7%

    Adverse Events

    Time FrameAdverse events captured from the time of participant consent until 30 days after the last dose of drug.
    Adverse Event Reporting Description
    Arm/Group TitlePhase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Arm/Group DescriptionBendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 20 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 30 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 40 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine, Fludarabine + Rituximab Bendamustine: Phase 1: 50 mg/m^2 IV on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1Bendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab Phase 2: 30 mg/m^2 by vein (fixed) on Days 1,2,3 (after fludarabine) Fludarabine: Course 1: 20 mg/m^2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m^2 IV, Days 1,2,3 Rituximab: Course 1: 375 mg/m^2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m^2 IV, Day 1
    All Cause Mortality
    Phase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/6 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/30 (3.3%)
    Serious Adverse Events
    Phase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/6 (66.7%) 0/3 (0%) 4/6 (66.7%) 5/6 (83.3%) 16/30 (53.3%)
    Blood and lymphatic system disorders
    Hemolysis0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Neutropenia1/6 (16.7%) 10/3 (0%) 01/6 (16.7%) 10/6 (0%) 01/30 (3.3%) 1
    Elevated BUN0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Hemorrhage0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Hemorrhage Bladder0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Subdural Hematoma0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Thrombocytopenia1/6 (16.7%) 10/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Cardiac disorders
    Hypotension0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Gastrointestinal disorders
    Anorexia0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Dehydration2/6 (33.3%) 20/3 (0%) 00/6 (0%) 00/6 (0%) 02/30 (6.7%) 2
    Nausea and Vomiting3/6 (50%) 40/3 (0%) 00/6 (0%) 01/6 (16.7%) 12/30 (6.7%) 2
    Acites0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    General disorders
    Amloidosis0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Fainting0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Fall0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Fatigue1/6 (16.7%) 10/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Pain1/6 (16.7%) 10/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Chills0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Fever0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Growth Neck0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Infections and infestations
    Cellulitis0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Infection1/6 (16.7%) 10/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Neutropenic Fever1/6 (16.7%) 10/3 (0%) 02/6 (33.3%) 41/6 (16.7%) 16/30 (20%) 7
    Pneumonia0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 13/30 (10%) 3
    Bladder Infection0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Sepsis0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Urinary Tract Infection0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Investigations
    Drug Rash0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 2
    Tumor Flare0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Allergic Reaction Investigational Product0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Metabolism and nutrition disorders
    Tumor Lysis0/6 (0%) 00/3 (0%) 02/6 (33.3%) 21/6 (16.7%) 13/30 (10%) 3
    Hyperphosphatemia0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Musculoskeletal and connective tissue disorders
    Gout1/6 (16.7%) 10/3 (0%) 00/6 (0%) 00/6 (0%) 00/30 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous Cell Carcinoma0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 00/30 (0%) 0
    Renal and urinary disorders
    Renal Failure0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 01/30 (3.3%) 1
    Vascular disorders
    Phlebitis0/6 (0%) 00/3 (0%) 00/6 (0%) 01/6 (16.7%) 10/30 (0%) 0
    Other (Not Including Serious) Adverse Events
    Phase 1 20 mg/m^2Phase 1 30 mg/m^2Phase 1 40 mg/m^2Phase 1 50 mg/m^2Phase 2
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total6/6 (100%) 3/3 (100%) 6/6 (100%) 6/6 (100%) 30/30 (100%)
    Blood and lymphatic system disorders
    Neutropenia0/6 (0%) 02/3 (66.7%) 24/6 (66.7%) 43/6 (50%) 323/30 (76.7%) 33
    Hyperglycemia2/6 (33.3%) 23/3 (100%) 30/6 (0%) 02/6 (33.3%) 230/30 (100%) 30
    Thrombocytopenia0/6 (0%) 00/3 (0%) 01/6 (16.7%) 11/6 (16.7%) 115/30 (50%) 32
    Anemia0/6 (0%) 00/3 (0%) 01/6 (16.7%) 11/6 (16.7%) 17/30 (23.3%) 7
    Cardiac disorders
    Atrial Fibrillation0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 02/30 (6.7%) 2
    Gastrointestinal disorders
    Dehydration0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 03/30 (10%) 3
    Nausea4/6 (66.7%) 43/3 (100%) 33/6 (50%) 32/6 (33.3%) 218/30 (60%) 18
    Vomiting0/6 (0%) 00/3 (0%) 00/6 (0%) 03/6 (50%) 32/30 (6.7%) 2
    Anorexia1/6 (16.7%) 11/3 (33.3%) 10/6 (0%) 03/6 (50%) 33/30 (10%) 3
    General disorders
    Fatigue1/6 (16.7%) 11/3 (33.3%) 12/6 (33.3%) 23/6 (50%) 330/30 (100%) 30
    Edema1/6 (16.7%) 10/3 (0%) 00/6 (0%) 00/6 (0%) 02/30 (6.7%) 2
    Infections and infestations
    Infection0/6 (0%) 00/3 (0%) 04/6 (66.7%) 44/6 (66.7%) 410/30 (33.3%) 17
    Metabolism and nutrition disorders
    Tumor Lysis0/6 (0%) 00/3 (0%) 01/6 (16.7%) 10/6 (0%) 02/30 (6.7%) 2
    Vascular disorders
    Deep Vein Thrombosis0/6 (0%) 00/3 (0%) 00/6 (0%) 00/6 (0%) 04/30 (13.3%) 4

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT 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/TitleWilliam Wierda, MD./Professor
    OrganizationThe University of Texas MD Anderson Cancer Center
    Phone713-745-0428
    EmailCR_Study_Registration@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01096992
    Other Study ID Numbers:
    • 2009-0546
    • NCI-2011-01942
    First Posted:
    Mar 31, 2010
    Last Update Posted:
    Sep 25, 2019
    Last Verified:
    Sep 1, 2019