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

Recurrent Small Lymphocytic Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089154
• Other study ID #: NCI-2012-01454
• Secondary ID: OSU 0410CLLRC-OS
• Status: Completed
• Phase: Phase 2
• First received: August 4, 2004
• Last updated: July 15, 2013
• Start date: August 2004

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• 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

Biological:
• apolizumab
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Chronic Lymphocytic Leukemia Research Consortium (CRC)	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (CR+PR)		Up to 3 years	No
Primary	Progression-free survival rate		Up to 3 years	No
Primary	Frequency and severity of treatment-related adverse events		Up to 30 days	Yes
Secondary	Pharmacokinetic clearance		Days 1, 2, 3, 5, 8, 15, 22, 26, 27, 29 and 1, 2, 3, and 6 months	No