Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

June 3, 2013 updated by: National Cancer Institute (NCI)

Phase I Study of Thrice Weekly Hu1D10*in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Acute Leukemia

Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have chronic lymphocytic leukemia, lymphocytic lymphoma, acute lymphoblastic leukemia, or acute myeloid leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) or biological effective dose of monoclonal antibody Hu1D10 (apolizumab) in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma.

II. Determine the safety of this drug, in terms of frequency and severity of treatment-related adverse events, in this patient population.

SECONDARY OBJECTIVES:

I. Determine whether this drug has anti-leukemia/lymphoma activity in patients expressing the Hu1D10 antigen.

II. Determine the pharmacokinetics of this drug in this patient population. III. Determine whether the infusion-related toxicity of this drug is secondary to cytokine release in these patients.

IV. Determine whether the intensity of 1D10 target antigen on tumor cells is related to clinical response and treatment toxicity in these patients.

V. Determine the pharmacodynamics of this drug in this patient population.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to diagnosis (chronic lymphocytic leukemia or small lymphocytic lymphoma vs acute lymphoblastic leukemia [ALL] or acute myeloid leukemia [AML]). Patients with ALL or AML are enrolled after the maximum tolerated dose (MTD) is determined.

Patients receive apolizumab IV over at least 2 hours on days 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a complete or partial response who relapse after 2 months may receive an additional course of therapy provided they still express the 1D10 antigen.

Cohorts of 3-6 patients receive escalating doses of MOAB Hu1D10 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity (DLT). If no DLT is observed, the biological effective dose (BED) is determined in the above cohorts. The BED is defined as the dose at which at least 4 of 6 patients experience an acceptable minimum trough level and clinical response. An additional 24 patients (12 per stratum) are treated at the MTD.

Patients are followed at 1 week, 1 and 2 months, and then every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 35 patients (12 per stratum) will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • One of the following diagnoses:

    • Histologically confirmed chronic lymphocytic leukemia (CLL) or non-contiguous stage II or stage III-IV small lymphocytic lymphoma (SLL)

      • Previously treated with at least 1 form of chemotherapy or immunotherapy

    • Histologically confirmed acute lymphoblastic leukemia (enrolled after the maximum tolerated dose (MTD) is determined)

      • Must have failed 1 prior therapy
      • Ineligible for allogeneic stem cell transplantation

    • Histologically confirmed acute myeloid leukemia (enrolled after the MTD is determined)

      • Primary refractory or relapsed (within the past year) disease
      • Ineligible for potential curative therapy

  • Express Hu1D10 antigen

    • Greater than 2 times the mean fluorescence intensity of the control by flow cytometry (blood or bone marrow cells) OR
    • Positive by immunohistochemical staining (lymph node)

  • Presenting with one of the following indications for treatment unless early bone marrow transplantation is planned (CLL or SLL patients only):

    • Disease-related progressive symptoms
    • Progressively worsening anemia or thrombocytopenia
    • Progressively worsening lymphadenopathy
    • Massive splenomegaly or hypersplenism
    • Hyperlymphocytosis (WBC greater than 200,000/mm3) or lymphocyte doubling time less than 12 months
    • Marrow failure secondary to marrow infiltration by leukemia or lymphoma
  • Performance status - ECOG 0-2
  • At least 2 years
  • See Disease Characteristics
  • Platelet count at least 50,000/mm^3 (without transfusion)
  • Bilirubin no greater than 3 mg/dL (unless elevated secondary to tumor)
  • Creatinine no greater than 2.0 mg/dL
  • No prior decompensated congestive heart failure, unstable angina, or myocardial infarction within the past 6 months not corrected by percutaneous transluminal coronary angioplasty or surgery
  • No active infection requiring oral or IV antibiotics
  • No other malignancy that would limit life expectancy
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study
  • See Disease Characteristics
  • At least 1 month since prior rituximab or alemtuzumab (unless CD20 or CD52 antigen is expressed on tumor cells)
  • No prior monoclonal antibody Hu1D10
  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Patients receive apolizumab IV over at least 2 hours on days 1, 2, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a complete or partial response who relapse after 2 months may receive an additional course of therapy provided they still express the 1D10 antigen.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Names:
  • pharmacological studies
Biological: apolizumab
Given IV
Other Names:
  • 1D1O Anti-lymphoma Antibody
  • MOAB 1D10
  • MoAb Hu1D10
  • Monoclonal antibody 1D10
  • Monoclonal Antibody Hu1D10

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MTD defined as the dose level below which two or more of six patients experience a DLT assessed using NCI CTC version 2.0
Time Frame: Up to 30 days
Up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of the degree of apoptosis induced by ex vivo incubation of human CLL cells with Hu1D10
Time Frame: Up to 1 year
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data. Nevertheless, low statistical power will greatly limit these analyses.
Up to 1 year
Cytokine release
Time Frame: Up to 1 year
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data. Nevertheless, low statistical power will greatly limit these analyses.
Up to 1 year
Caspase activation
Time Frame: Up to 1 year
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data. Nevertheless, low statistical power will greatly limit these analyses.
Up to 1 year
Signaling and expression of apoptosis protein
Time Frame: Up to 1 year
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data. Nevertheless, low statistical power will greatly limit these analyses.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2001

Primary Completion (Actual)

April 1, 2006

Study Registration Dates

First Submitted

June 6, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 4, 2013

Last Update Submitted That Met QC Criteria

June 3, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01405
  • U01CA076576 (U.S. NIH Grant/Contract)
  • OSU 0101
  • OSU-0101
  • NCI-1254
  • OSU-00H0230
  • CDR0000068695

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Recurrent Adult Acute Myeloid Leukemia

Clinical Trials on laboratory biomarker analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe