Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

August 20, 2013 updated by: Case Comprehensive Cancer Center

A Phase I Trial of Bendamustine Plus Alemtuzumab for the Treatment of Fludarabine Refractory Chronic Lymphocytic Leukemia

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
      • Cleveland, Ohio, United States, 44106
        • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Bendamustine plus Alemtuzumab
Drug: Bendamustine Hydrochloride
Bendamustine 70 mg/m2 IV Day 8 and 9 every 28 days for 6 courses of therapy
Other Names:
  • Treanda
  • SDX-105
  • Ribomustin
  • cytostasan hydrochloride
Biological: Alemtuzumab
Given subcutaneously (SC)on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.
Other Names:
  • Campath
  • Campath-1H
  • anti-CD52 monoclonal antibody
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the safety of the combination of alemtuzumab and bendamustine in patients with advanced CLL
Time Frame: up to 1 year
AEs will be graded according to the NCI CTCAE, Version 3.0.
up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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/m2 day 8 and 9 monthly.
Time Frame: up to 12 weeks
Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.
up to 12 weeks
Clinical activity and response of the combination of bendamustine hydrochloride and alemtuzumab
Time Frame: up to 1 year
Examined by summarizing response overall and by cohort as frequency counts and percentages. Response criteria as described by the National Cancer Institute-sponsored Working Group Guidelines.
up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Collaborators

Cephalon

Investigators

  • Principal Investigator: Matt Kalaycio, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (ACTUAL)

September 1, 2012

Study Completion (ACTUAL)

March 1, 2013

Study Registration Dates

First Submitted

July 24, 2009

First Submitted That Met QC Criteria

July 27, 2009

First Posted (ESTIMATE)

July 28, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

August 22, 2013

Last Update Submitted That Met QC Criteria

August 20, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE1907
  • NCI-2010-00272 (OTHER: NCI/CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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