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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Noncontiguous Stage II Small Lymphocytic Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Stage III Small Lymphocytic Lymphoma, Stage IV Small Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: apolizumab
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (apolizumab)<br>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<br>* Given IV<br>* Other names: Monoclonal Antibody Hu1D10;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

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