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

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: Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Biological: apolizumab

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

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

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

How is the study designed?

Design Details

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

Number of Arms

1

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)	Up to 3 years
Progression-free survival rate	Up to 3 years
Frequency and severity of treatment-related adverse events	Up to 30 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

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: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: NCI-2012-01454; OSU 0410; CLLRC-OSU-0410; CDR0000378072; OSU-0410; NCI-6257; R21CA091564 (NIH)