Apolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

July 15, 2013 updated by: National Cancer Institute (NCI)

A Phase II Study of Thrice Weekly Apolizumab in Patients With Chronic Lymphocytic Leukemia : CRC Master Protocol

This phase II trial is studying how well apolizumab works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Monoclonal antibodies such as apolizumab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the response rate and progression-free survival rate in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or noncontiguous stage II or stage III or IV small lymphocytic lymphoma treated with apolizumab.

II. Determine the safety of this drug, in terms of the frequency and severity of treatment-related adverse events, in these patients.

SECONDARY OBJECTIVES:

I. Determine clinical response to apolizumab varies by genetic subtype of CLL. II. Determine if pharmacokinetic clearance is truly predicted by 1D10 antigen density on the individual patient CLL cell and how apolizumab clearance correlates with response and selected toxicities observed.

III. To determine the importance of reactive oxygen species and specific signaling pathways in promoting apolizumab-mediated apoptosis in vitro and in vivo in primary CLL cells and if this correlates with clinical response to therapy.

IV. To determine the cellular properties which convey resistance to apolizumab in CLL in vivo.

OUTLINE: This is a multicenter study.

Patients receive apolizumab IV over 2-4 hours on days 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 week, at 1 and 2 months, every 3 months for 1 year, and then every 6 months for 3 years.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

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
    • California
      • La Jolla, California, United States, 92093-0820
        • Chronic Lymphocytic Leukemia Research Consortium (CRC)
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical 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

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed hematologic malignancy of 1 of the following histologies:

    • Chronic lymphocytic leukemia (CLL)

    • Small lymphocytic lymphoma (SLL)

      • Noncontiguous stage II or stage III or IV disease

  • Received >= 1 form of prior immunotherapy or chemotherapy

    • Completed therapy at least 4 weeks ago

  • Requires therapy (unless early bone marrow transplantation is planned), as indicated by 1 of the following criteria:

    • Progressively worsening disease (symptoms increasing in severity by 1 toxicity criterion over a period of >= 2 weeks)
    • Progressively worsening anemia or thrombocytopenia
    • Progressively worsening lymphadenopathy
    • Massive splenomegaly or hypersplenism
    • Hyperlymphocytosis (WBC > 200,000/mm^3) OR lymphocyte doubling time < 12 months
    • Marrow failure due to marrow infiltration by leukemia or lymphoma
  • Leukemia cells must express 1D10 antigen > 2 times mean fluorescent intensity of the control by flow cytometry of blood or bone marrow cells
  • Performance status - ECOG 0-2
  • At least 2 years
  • Platelet count >= 50,000/mm^3 (transfusion independent)
  • Bilirubin =< 3 mg/dL (unless due to tumor involvement)
  • Creatinine =< 2.0 mg/dL
  • No decompensated congestive heart failure
  • No unstable angina
  • No myocardial infarction within the past 6 months not corrected by surgery or percutaneous transluminal coronary angioplasty
  • No active infection requiring oral or IV antibiotics
  • No other malignancy that limits life expectancy to < 2 years or that requires active anticancer therapy within 4 weeks of study entry
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after study treatment
  • Recovered from prior immunotherapy
  • More than 3 months since prior alemtuzumab or rituximab
  • No prior apolizumab
  • Recovered from prior chemotherapy
  • More than 4 weeks since prior anticancer hormonal therapy
  • More than 4 weeks since prior anticancer radiotherapy
  • More than 4 weeks since prior anticancer surgery
  • At least 4 weeks since other prior therapy for CLL or SLL and recovered

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (apolizumab)
Patients receive apolizumab IV over 2-4 hours on days 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in the absence of disease progression or unacceptable toxicity.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Biological: apolizumab
Given IV
Other Names:
  • 1D1O Anti-lymphoma Antibody
  • MOAB 1D10
  • MoAb Hu1D10
  • Monoclonal antibody 1D10
  • Monoclonal Antibody Hu1D10

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate (CR+PR)
Time Frame: Up to 3 years
Up to 3 years
Progression-free survival rate
Time Frame: Up to 3 years
Up to 3 years
Frequency and severity of treatment-related adverse events
Time Frame: Up to 30 days
Up to 30 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic clearance
Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 26, 27, 29 and 1, 2, 3, and 6 months
Days 1, 2, 3, 5, 8, 15, 22, 26, 27, 29 and 1, 2, 3, and 6 months

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

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

August 1, 2004

Primary Completion (ACTUAL)

October 1, 2005

Study Registration Dates

First Submitted

August 4, 2004

First Submitted That Met QC Criteria

August 4, 2004

First Posted (ESTIMATE)

August 5, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

July 16, 2013

Last Update Submitted That Met QC Criteria

July 15, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01454
  • OSU 0410
  • CLLRC-OSU-0410
  • CDR0000378072
  • OSU-0410
  • NCI-6257
  • R21CA091564 (NIH)

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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