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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00089154

Collaborator

(none)

Enrollment

Locations

Arm

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.
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.
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 Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2004

Actual Primary Completion Date :

Oct 1, 2005

Arms and Interventions

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.	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 Names: pharmacological studies

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.

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 Names:

pharmacological studies

Outcome Measures

Primary Outcome Measures

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

Pharmacokinetic clearance [Days 1, 2, 3, 5, 8, 15, 22, 26, 27, 29 and 1, 2, 3, and 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Chronic Lymphocytic Leukemia Research Consortium (CRC)	La Jolla	California	United States	92093-0820
2	Ohio State University Medical Center	Columbus	Ohio	United States	43210