Expired Study
This study is not currently recruiting Study Participants on ClinicalConnection.com. If you would like to find active studies please search for clinical trials.

Columbus, Ohio 43210


Purpose:

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 summary:

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.


Criteria:

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 is Available At:


Original ID:

NCI-2012-01405


NCT ID:

NCT00017472


Secondary ID:

OSU 0101


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 1


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety Study, Interventi


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

35


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:John Byrd
Principal Investigator
Ohio State University

Study Dates

Start Date:April 2001
Primary Completion Date:April 2006
Primary Completion Type:Actual
Verification Date:June 2013
Last Changed Date:June 3, 2013
First Received Date:June 6, 2001

Study Outcomes

Outcome Type:Primary Outcome
Measure: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
Safety Issues:True
Outcome Type:Secondary Outcome
Measure:Evaluation of the degree of apoptosis induced by ex vivo incubation of human CLL cells with Hu1D10
Time Frame:Up to 1 year
Safety Issues:False
Description: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 analyse
Outcome Type:Secondary Outcome
Measure:Cytokine release
Time Frame:Up to 1 year
Safety Issues:False
Description: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 analyse
Outcome Type:Secondary Outcome
Measure:Caspase activation
Time Frame:Up to 1 year
Safety Issues:False
Description: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 analyse
Outcome Type:Secondary Outcome
Measure:Signaling and expression of apoptosis protein
Time Frame:Up to 1 year
Safety Issues:False
Description: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 analyse

Study Interventions

Intervention Type:Biological
Name:apolizumab
Description:Given IV
Arm Name:Arm I
Other Name:1D1O Anti-lymphoma Antibody
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Arm I
Intervention Type:Other
Name:pharmacological study
Description:Correlative studies
Arm Name:Arm I
Other Name:pharmacological studies

Study Arms

Study Arm Type:Experimental
Arm Name:Arm I
Description: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.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Lin TS, Stock W, Xu H, Phelps MA, Lucas MS, Guster SK, Briggs BR, Cheney C, Porcu P, Flinn IW, Grever MR, Dalton JT, Byrd JC. A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia. Leuk Lymphoma. 2009 Dec;50(12):1958-63.
PMID:19860603

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


This study is not currently recruiting Study Participants. The form below is not enabled.