Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

This study has been terminated.
(No more eligible patients)
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00947388
First received: July 24, 2009
Last updated: August 20, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: Bendamustine Hydrochloride
Biological: Alemtuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Bendamustine Plus Alemtuzumab for the Treatment of Fludarabine Refractory Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Evaluate the safety of the combination of alemtuzumab and bendamustine in patients with advanced CLL [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    AEs will be graded according to the NCI CTCAE, Version 3.0.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.

  • Clinical activity and response of the combination of bendamustine hydrochloride and alemtuzumab [ Time Frame: up to 1 year ] [ Designated as safety issue: No ]
    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.


Enrollment: 9
Study Start Date: November 2008
Study Completion Date: March 2013
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • bendamustine Hydrochloride
  • cytostasan hydrochloride
  • Ribomustin
  • SDX-105
  • Treanda
Biological: Alemtuzumab
Given subcutaneously (SC)on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26.
Other Names:
  • anti-CD52 monoclonal antibody
  • Campath
  • Campath-1H
  • MoAb CD52
  • Monoclonal Antibody Campath-1H
  • Monoclonal Antibody CD52

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00947388

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Case Comprehensive Cancer Center
Cephalon
Investigators
Principal Investigator: Matt Kalaycio, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Paolo Caimi, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00947388     History of Changes
Other Study ID Numbers: CASE1907, NCI-2010-00272
Study First Received: July 24, 2009
Last Updated: August 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:
Refractory Chronic Lymphocytic Leukemia
Bendamustine
Alemtuzumab
Phase I
CLL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Antibodies, Monoclonal
Campath 1G
Antibodies, Neoplasm
Bendamustine
Alemtuzumab
Nitrogen Mustard Compounds
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 28, 2014