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LeukemiaPhase 1/2NCT01096992

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

A Phase 1/2 study testing Bendamustine, Fludarabine and Rituximab in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Leukemia
What is being tested?
Bendamustine, Fludarabine and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteUnited States
Study dates
19 Apr 2010to 31 Mar 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have a diagnosis of CLL/Small Lymphocytic Lymphoma (SLL) and be previously treated
  • Patients must have an indication for treatment by 2008 IWCLL Criteria
  • Age >/= 16 years
  • Zubrod performance status </= 2
  • 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
  • Patients must give written informed consent
  • Patients of childbearing potential must be willing to practice birth control during the study

Who cannot join

  • Pregnant or breast-feeding females
  • Significant co-morbidity indicated by major organ system dysfunction
  • Active, uncontrolled infection, including active hepatitis
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or immune thrombocytopenia purpura (ITP)
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I/II Clinical Trial of Fludarabine, Bendamustine, and Rituximab (FBR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)

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.

Read the 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.

Conditions
Leukemia
Keywords
Chronic lymphocytic leukemia, CLL, Bendamustine, Fludarabine, Fludara, Fludarabine Phosphate, Rituximab, Rituxan
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    Also called Bendamustine HCI, Bendamustine Hydrochloride, CEP-18083, SDX-105

    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)

  • FludarabineDrug

    Also called Fludara, Fludarabine Phosphate

    Course 1: 20 mg/m2 intravenous (IV) on Days 2,3,4 Courses 2-6: 20 mg/m2 IV, Days 1,2,3

  • RituximabDrug

    Also called Rituxan

    Course 1: 375 mg/m2 IV, Day 4 (after fludarabine) Courses 2-6: 500 mg/m2 IV, Day 1

Study groups in NCT01096992
Study groupRoleWhat they receive
Phase 1 20 mg/m^2ExperimentalBendamustine, Fludarabine + Rituximab
Receives: Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab
Phase 2ExperimentalBendamustine 30 mg/m^2 by vein (fixed), Days 1,2,3 + Fludarabine + Rituximab
Receives: Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab
Phase 1 30 mg/m^2ExperimentalBendamustine, Fludarabine + Rituximab
Receives: Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab
Phase 1 40 mg/m^2ExperimentalBendamustine, Fludarabine + Rituximab
Receives: Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab
Phase 1 50 mg/m^2ExperimentalBendamustine, Fludarabine + Rituximab
Receives: Drug: Bendamustine; Drug: Fludarabine; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR)

    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.

    Measured: After 4 week cycle

Secondary outcomes (1)
  1. Overall Response Rate of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR)

    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;

    Measured: Overall response assessed 2 months after 6th or last course if participants not able to receive all 6 intended courses of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2010 (estimated)
  2. Study start19 Apr 2010
  3. Primary completion31 Mar 2017
  4. Study completion31 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01096992
Sponsor's protocol ID
2009-0546
Other IDs
NCI-2011-01942
Status last verified
Sep 2019
First submitted
30 Mar 2010
Last updated
25 Sep 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bendamustine, Fludarabine and Rituximab in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD) of Bendamustine Combined With Fixed-Dose Fludarabine and Rituximab (FBR) (time frame: After 4 week cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.

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