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


Phase 1
18 Years
N/A
Not Enrolling
Both
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Splenic Marginal Zone Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Small Lymphocytic Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

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

Outcome Time Frame:

Up to 30 days

Safety Issue:

Yes

Principal Investigator

John Byrd

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01405

NCT ID:

NCT00017472

Start Date:

April 2001

Completion Date:

Related Keywords:

  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncontiguous Stage II Marginal Zone Lymphoma
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Splenic Marginal Zone Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Small Lymphocytic Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone

Name

Location
Ohio State University Medical Center Columbus, Ohio  43210