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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089154
First received: August 4, 2004
Last updated: July 15, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Noncontiguous Stage II Small Lymphocytic Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Stage III Small Lymphocytic Lymphoma
Stage IV Small Lymphocytic Lymphoma
Biological: apolizumab
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Thrice Weekly Apolizumab in Patients With Chronic Lymphocytic Leukemia : CRC Master Protocol

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (CR+PR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Frequency and severity of treatment-related adverse events [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic clearance [ Time Frame: Days 1, 2, 3, 5, 8, 15, 22, 26, 27, 29 and 1, 2, 3, and 6 months ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: August 2004
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: apolizumab
Given IV
Other Names:
  • 1D1O Anti-lymphoma Antibody
  • MOAB 1D10
  • MoAb Hu1D10
  • Monoclonal antibody 1D10
  • Monoclonal Antibody Hu1D10
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00089154

Locations
United States, California
Chronic Lymphocytic Leukemia Research Consortium (CRC)
La Jolla, California, United States, 92093-0820
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: John Byrd Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089154     History of Changes
Other Study ID Numbers: NCI-2012-01454, OSU 0410, CLLRC-OSU-0410, CDR0000378072, OSU-0410, NCI-6257, R21CA091564
Study First Received: August 4, 2004
Last Updated: July 15, 2013
Health Authority: United States: Food and Drug Administration

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
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014