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Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL

Phase 1
18 Years
Not Enrolling
Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia

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Trial Information

Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL

While recurrent non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are
often responsive to therapy, they are rarely curable and disease control is the primary
therapeutic goal. Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown single
agent activity in these diseases and is currently approved for the therapy of recurrent
indolent lymphoma. However, rituximab induces objective remission in at most 60% of cases
with inevitable relapse. The 1D10 antigen, a subclass of the HLA-DR molecule, is expressed
in a majority of cases of B-cell malignancy. Apolizumab is a humanized monoclonal antibody
that targets this antigen. In a phase I dose escalation trial this antibody has shown
clinical activity against B-cell NHL that express the 1D10 antigen. Acute infusional
toxicity has been tolerable, and a maximum of 5 mg/kg has been given in each of 4 weekly
doses. Preclinical in vitro data from Dr. George Weiner's laboratory suggests at least
additive anti-tumor efficacy when cells are exposed to both antibodies simultaneously. This
trial will pilot the use of combination therapy with rituximab and apolizumab in patients
with tumors that express both antigens. Feasibility and tolerability of the regimen will be
determined. Experimental endpoints will include pharmacokinetics of apolizumab, assessment
of apoptosis in circulating CLL cells by FACS analysis with Annexin 5, assessment of T-and
B-cell dynamics, and effects of rituximab and apolizumab on CLL mRNA as measured by cDNA
microarray. Following the first 21 patients on trial, the administration sequence of
rituximab and apolizumab was changed from rituximab first to apolizumab first to potentially
reduce sensitization of apolizumab toxicity by rituximab.

Inclusion Criteria


Diagnosis of B-cell lymphoma, Waldenstrom's CLL with surface expression of both CD20 and
1D10 antigen by immunohistochemistry (IHC) or fluorescence of activated cell sorting
(FACS) with anti-CD20 and 1D10 antibody. Positive 1D10 expression in a FACS assay is
defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody
by FACS or greater than 20% of cells 1D10+ by IHC.

Confirmation of diagnosis in Laboratory of Pathology, NCI or OSU.

Prior therapy with at least one systemic treatment, and not a candidate for potentially
curative (i.e., transplant) treatment at the time of study entry. Prior treatment with
rituximab greater than or equal to 1 month ago is permitted.

Age greater than 18 years.

ECOG performance status less than or equal to 2.

Major organ function: ANC greater than or equal to 500/microliter, Platelet greater than
or equal 25,000/microliter, Creatinine less than or equal to 1.5 mg/dl or creatinine
clearance greater than 60 cc/min; SGPT less than 5 x upper limit of normal; bilirubin less
than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as
defined by greater than 80% unconjugated; unless impairment due to organ involvement by

Provides informed consent.


Pregnancy or nursing. Both male and female patients must be willing to use adequate

Prior apolizumab treatment.

SActive cardiac disease, cerebrovascular disease or peripheral arterial vascular disease.

Active CNS lymphoma.

Systemic cytotoxic chemotherapy within 3 weeks of enrollment or systemic steroids (except
stable doses less than 10 mg/day) within 1 week of enrollment.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) and toxicity of apolizumab.

Safety Issue:


Principal Investigator

Wyndham H Wilson, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

August 2001

Completion Date:

January 2010

Related Keywords:

  • Non-Hodgkin's Lymphoma
  • Chronic Lymphocytic Leukemia
  • HU 1D10
  • Rituximab
  • Lymphoma
  • Monoclonal Antibody
  • Non-Hodgkin's Lymphoma
  • NHL
  • Chronic Lymphocytic Leukemia
  • CLL
  • Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Non-Hodgkin



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