Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

NCT ID: NCT00947388

Last Updated: 2013-08-22

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

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2013-03-31

Brief Summary

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This phase I trial is studying the side effects and best dose of alemtuzumab when given together with bendamustine hydrochloride in treating patients with relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that did not respond to fludarabine phosphate. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bendamustine hydrochloride together with alemtuzumab may kill more cancer cells.

Detailed Description

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PRIMARY OBJECTIVES:

I. Evaluate the safety of the combination of alemtuzumab and bendamustine (bendamustine hydrochloride) in patients with advanced CLL.

II. Establish the maximum tolerated dose of alemtuzumab up to the standard dose of 30mg thrice weekly when combined with bendamustine at a standard dose of 70 mg/m\^2 day 8 and 9 monthly.

III. Define a recommended dose for subsequent Phase II studies. IV. Evaluate preliminary evidence of activity as determined by response rates with correlation to EAS flow cytometry.

OUTLINE: This is a dose-escalation study of alemtuzumab.

Patients receive bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 8 and 9 for up to 6 courses in the absence of disease progression or unacceptable toxicity and alemtuzumab subcutaneously (SC) on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.

After completion of study treatment, patients are followed every 3 months for 1 year.

Conditions

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Recurrent Small Lymphocytic Lymphoma Refractory Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage III Small Lymphocytic Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Small Lymphocytic Lymphoma

Keywords

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Refractory Chronic Lymphocytic Leukemia Bendamustine Alemtuzumab Phase I CLL

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bendamustine plus Alemtuzumab

Group Type EXPERIMENTAL

Bendamustine Hydrochloride

Intervention Type DRUG

Bendamustine 70 mg/m2 IV Day 8 and 9 every 28 days for 6 courses of therapy

Alemtuzumab

Intervention Type BIOLOGICAL

Given subcutaneously (SC)on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.

Interventions

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Bendamustine Hydrochloride

Bendamustine 70 mg/m2 IV Day 8 and 9 every 28 days for 6 courses of therapy

Intervention Type DRUG

Alemtuzumab

Given subcutaneously (SC)on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.

Intervention Type BIOLOGICAL

Other Intervention Names

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cytostasan hydrochloride Ribomustin SDX-105 Treanda anti-CD52 monoclonal antibody Campath Campath-1H MoAb CD52 Monoclonal Antibody Campath-1H Monoclonal Antibody CD52

Eligibility Criteria

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Inclusion Criteria

1. Patients with CLL or SLL as defined by the WHO classification system with indications for treatment by National Cancer Institute (NCI) Working Group criteria.
2. Measurable disease (lymphocytes equal or greater than 5,000/µL, or measurable lymphadenopathy, or bone marrow involvement greater than 30%).
3. Males and females 18 years of age or older.
4. Patients must be relapsed or refractory and have been treated with a minimum of one prior purine analog-based chemotherapy regimen (e.g., fludarabine, cladribine, or pentostatin).
5. All previous cancer therapies, radiation, hormonal therapy and surgery, must have been discontinued at least 28 days prior to the start of treatment. Any cytotoxic chemotherapy must have been discontinued 28 days prior to the start of treatment. Acute toxicities from prior therapy must have resolved to Grade ≤ 1 above baseline.
6. Normal oxygen saturation with pulse oximetry on room air.
7. Hemoglobin 9 or greater gm/dL (may be post-transfusion).
8. Platelet count 50 x103/mL or greater
9. Total bilirubin less than 2 X ULN, and ALT and AST less than 2 x ULN.
10. Serum creatinine 2 X ULN or less. In addition, the calculated glomerular filtration rate (GFR) must be \> 30cc/min.
11. ECOG Performance Status 2 or less.
12. Anticipated survival of at least 3 months.
13. For men and women of child-producing potential, use of effective contraceptive methods during the study and for one month after discontinuation of treatment.

Exclusion Criteria

1. Pregnant or lactating women.
2. Severe chronic obstructive pulmonary disease with hypoxemia or an uncorrectable pulmonary compromise.
3. Seizures not controlled by anticonvulsant therapy.
4. Participation in any investigational drug study within 28 days before study entry.
5. Patients with second malignancy requiring active treatment.
6. Active, symptomatic bacterial, fungal, or viral infection including active HIV or viral (A, B, or C) hepatitis.
7. Clinically significant bleeding event within the last 3 months, unrelated to trauma, or underlying condition that would be expected to result in a bleeding diathesis.
8. Patients with life- or function-threatening CLL complications (e.g., cord compression, hemolytic crisis, urinary tract obstruction).
9. Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any of the study's endpoints.
10. Systemic treatment for CLL/SLL within 28 days of study entry
11. Subjects with a history of leukemic meningitis, or signs and symptoms suggestive of leukemic meningitis, must have a negative lumbar puncture within 2 weeks of study entry.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Cephalon

INDUSTRY

Sponsor Role collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matt Kalaycio, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Paolo Caimi, MD

Role: PRINCIPAL_INVESTIGATOR

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Locations

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Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-00272

Identifier Type: OTHER

Identifier Source: secondary_id

CASE1907

Identifier Type: -

Identifier Source: org_study_id