Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

NCT00947388 | Terminated Phase 1 DMC

• 2 other identifiers: CASE1907NCI-2010-00272
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

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

Refractory Chronic Lymphocytic Leukemia; Bendamustine; Alemtuzumab; Phase I; CLL

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety of the combination of alemtuzumab and bendamustine in patients with advanced CLL

  AEs will be graded according to the NCI CTCAE, Version 3.0.

  up to 1 year

Secondary Outcomes (2)

• 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.

  up to 12 weeks

• Clinical activity and response of the combination of bendamustine hydrochloride and alemtuzumab

  up to 1 year

Study Arms (1)

Bendamustine plus Alemtuzumab

EXPERIMENTAL

Drug: Bendamustine Hydrochloride; Biological: Alemtuzumab

Interventions

Bendamustine Hydrochloride DRUG

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

Also known as: cytostasan hydrochloride, Ribomustin, SDX-105, Treanda

Bendamustine plus Alemtuzumab

Alemtuzumab BIOLOGICAL

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

Also known as: anti-CD52 monoclonal antibody, Campath, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H, Monoclonal Antibody CD52

Bendamustine plus Alemtuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with CLL or SLL as defined by the WHO classification system with indications for treatment by National Cancer Institute (NCI) Working Group criteria.
• Measurable disease (lymphocytes equal or greater than 5,000/µL, or measurable lymphadenopathy, or bone marrow involvement greater than 30%).
• Males and females 18 years of age or older.
• 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).
• 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.
• Normal oxygen saturation with pulse oximetry on room air.
• Hemoglobin 9 or greater gm/dL (may be post-transfusion).
• Platelet count 50 x103/mL or greater
• Total bilirubin less than 2 X ULN, and ALT and AST less than 2 x ULN.
• Serum creatinine 2 X ULN or less. In addition, the calculated glomerular filtration rate (GFR) must be \> 30cc/min.
• ECOG Performance Status 2 or less.
• Anticipated survival of at least 3 months.
• For men and women of child-producing potential, use of effective contraceptive methods during the study and for one month after discontinuation of treatment.

You may not qualify if:

• Pregnant or lactating women.
• Severe chronic obstructive pulmonary disease with hypoxemia or an uncorrectable pulmonary compromise.
• Seizures not controlled by anticonvulsant therapy.
• Participation in any investigational drug study within 28 days before study entry.
• Patients with second malignancy requiring active treatment.
• Active, symptomatic bacterial, fungal, or viral infection including active HIV or viral (A, B, or C) hepatitis.
• 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.
• Patients with life- or function-threatening CLL complications (e.g., cord compression, hemolytic crisis, urinary tract obstruction).
• 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.
• Systemic treatment for CLL/SLL within 28 days of study entry
• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• Cephalon: collaborator

Study Sites (2)

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

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bendamustine Hydrochloride; Alemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2009
• First Posted: July 28, 2009
• Study Start: November 1, 2008
• Primary Completion: September 1, 2012
• Study Completion: March 1, 2013
• Last Updated: August 22, 2013

Record last verified: 2013-08

Locations

US (2)