Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia

NCT ID: NCT00086775

Last Updated: 2013-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2003-07-31

Study Completion Date

2009-10-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab and rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. It is not yet known whether fludarabine is more effective when combined with alemtuzumab or with rituximab in treating chronic lymphocytic leukemia.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining fludarabine with either alemtuzumab or rituximab in treating patients who have refractory or relapsed B-cell chronic lymphocytic leukemia.

Detailed Description

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OBJECTIVES:

Primary

* Compare the complete response rate in patients with refractory or relapsed B-cell chronic lymphocytic leukemia treated with fludarabine and alemtuzumab vs fludarabine and rituximab.

Secondary

* Compare the overall response rate in patients treated with these regimens.
* Compare 1-year survival of patients treated with these regimens.
* Compare time to progression in patients treated with these regimens.
* Compare duration of response in patients treated with these regimens.
* Compare the adverse event profile of these regimens in these patients.
* Compare the molecular response rate in patients treated with these regimens.
* Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens.
* Compare the time to complete response in patients treated with these regimens.
* Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior treatment with fludarabine (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. At least 30 minutes before fludarabine administration, patients receive alemtuzumab subcutaneously (SC) on days 1-5.
* Arm II: Patients receive fludarabine as in arm I. At least 30 minutes before fludarabine administration, patients receive rituximab IV on days 1 and 4 of course 1 and on day 1 only in subsequent courses.

In both arms, treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. An interim assessment is performed during course 4. Patients achieving a partial response or stable disease receive 2 additional courses of therapy (for a total of 6 courses). Patients achieving a complete response (CR) do not receive further treatment beyond CR.

Patients are followed weekly for 2 months, monthly for 6 months, every 2 months for 6 months, and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.

Conditions

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Leukemia

Keywords

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refractory chronic lymphocytic leukemia B-cell chronic lymphocytic leukemia

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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alemtuzumab

Intervention Type BIOLOGICAL

rituximab

Intervention Type BIOLOGICAL

fludarabine phosphate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as:

* Peripheral lymphocyte count \> 5,000/mm\^3
* Clonal CD5-, CD19-, and CD23-positive lymphocytes
* Refractory to OR relapsed after prior first-line therapy
* No CNS involvement with CLL

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-2

Life expectancy

* Not specified

Hematopoietic

* See Disease Characteristics

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Hepatitis B surface antigen negative
* Hepatitis C antibody negative

Renal

* Creatinine ≤ 1.5 times ULN

Immunologic

* No active cytomegalovirus
* No prior fludarabine-associated autoimmune hemolytic anemia or immune thrombocytopenic purpura
* No active infection requiring treatment with antibiotic, antiviral, or antifungal agents
* No prior significant allergic reaction to antibody therapies that required therapy to be discontinued
* HIV negative

Other

* No active secondary malignancy
* No other concurrent severe diseases or mental disorders
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 4 weeks since prior alemtuzumab and/or rituximab
* No prior bone marrow transplantation
* No concurrent thrombopoietin or pegfilgrastim

Chemotherapy

* More than 3 weeks since prior fludarabine

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* More than 3 months since prior investigational drugs
* No other concurrent cytotoxic therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role lead

Principal Investigators

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Ann S. LaCasce, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

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Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Jackson Oncology Associates, PLLC

Jackson, Mississippi, United States

Site Status

Cancer Institute of New Jersey at Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status

Western Pennsylvania Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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CDR0000365631

Identifier Type: REGISTRY

Identifier Source: secondary_id

BRLX-STA1-03-058

Identifier Type: -

Identifier Source: secondary_id

OHSU-HEM-03050-P

Identifier Type: -

Identifier Source: secondary_id

DMS-F0334

Identifier Type: -

Identifier Source: secondary_id

BRLX-FLUCAM106

Identifier Type: -

Identifier Source: org_study_id