Monoclonal Antibody Therapy in Treating Patients With Lymphoma, Waldenstrom's Macroglobulinemia, or Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00029367

Purpose

RATIONALE: Monoclonal antibodies such as apolizumab and rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of combining apolizumab and rituximab in treating patients who have lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia Lymphoma	Biological: apolizumab Biological: rituximab	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Combination Antibody Therapy With Apolizumab (1D10) And Rituximab (CD20) In Relapsed Lymphoma And CLL

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Rituximab Apolizumab

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum tolerated dose (MTD) and toxicity of apolizumab [ Designated as safety issue: Yes ]
Antitumor activity at the MTD at the end of study treatment [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:

Effects of treatment in patients with chronic lymphocytic leukemia (CLL) as measured by microarray profiling pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
Effects of treatment in patients with CLL on kinetics of apoptosis as measured by fluorescent-activated cell sorting (FACS) analysis of Annnexin 5 pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
Effects of treatment on T-cell and B-cell levels pre-treatment, during treatment, and at the end of study treatment [ Designated as safety issue: No ]

Study Start Date:	August 2001
Primary Completion Date:	May 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of apolizumab when administered with rituximab in patients with relapsed CD20 and 1D10-positive B-cell lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia.
Determine the toxicity of this regimen in these patients.
Determine the antitumor activity of this regimen in these patients.
Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation study of apolizumab.

Patients receive apolizumab IV over several hours on day 1 followed 24-36 hours later by rituximab IV. Treatment repeats every 7 days for 4 weeks. At 12 weeks after completion of treatment, patients with stable disease or a complete or partial response may receive additional treatment for up to 3 courses.

Cohorts of 2-6 patients receive escalating doses of apolizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 24 additional patients (12 with chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia and 12 with lymphoma) are treated at the MTD.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-69 patients will be accrued for this study within 12 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically and immunophenotypically confirmed B-cell lymphoma, Waldenstrom's macroglobulinemia, or chronic lymphocytic leukemia
CD20 and 1D10-positive by immunohistochemistry or fluorescence-activated cell sorting
Received at least 1 prior systemic treatment regimen
Ineligible for potentially curative therapy (i.e., transplantation)
No active CNS lymphoma

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 500/mm^3*
Platelet count at least 75,000/mm^3* NOTE: * Unless due to lymphoma

Hepatic:

Bilirubin less than 2 mg/dL (5 mg/dL in case of Gilbert's syndrome defined as more than 80% unconjugated)*
SGPT less than 5 times upper limit of normal* NOTE: * Unless due to lymphoma

Renal:

Creatinine no greater than 1.5 mg/dL* OR
Creatinine clearance greater than 60 mL/min* NOTE: * Unless due to lymphoma

Cardiovascular:

No active cardiac disease
No active cerebrovascular disease
No active peripheral arterial vascular disease

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 month since prior rituximab
No prior apolizumab

Chemotherapy:

More than 3 weeks since prior systemic cytotoxic chemotherapy
No concurrent chemotherapy

Endocrine therapy:

More than 1 week since prior systemic steroids (except stable doses of less than 10 mg/day)

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00029367

Locations

United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Kieron Dunleavy, MD

NCI - Metabolism Branch;MET

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Hegde U, White T, Stetler-Stevenson M, et al.: Phase I study of combination rituximab (CD20) and apolizumab (Hu1D10) monoclonal antibody therapy in previously treated B-cell lymphoma and chronic lymphocytic leukemia. [Abstract] Blood 100 (11 pt 1): A-1389, 2002.

Study ID Numbers:	CDR0000068975, NCI-01-C-0235, NCI-2410
Study First Received:	January 10, 2002
Last Updated:	February 5, 2009
ClinicalTrials.gov Identifier:	NCT00029367 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult Hodgkin lymphoma
Waldenstrom macroglobulinemia
refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma

recurrent adult immunoblastic large cell lymphoma
recurrent adult Burkitt lymphoma
AIDS-related peripheral/systemic lymphoma
recurrent mantle cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:

Leukemia, Lymphoid
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Hemostatic Disorders
Leukemia
Hemorrhagic Disorders
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Cardiovascular Diseases
Lymphoma
Immunoproliferative Disorders

Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Rituximab
Vascular Diseases
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Waldenstrom Macroglobulinemia
Lymphoproliferative Disorders
Leukemia, B-Cell
Antirheumatic Agents
Neoplasms, Plasma Cell

ClinicalTrials.gov processed this record on November 27, 2009