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A Phase 1-2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

2014-08-27 03:15:12 | BioPortfolio

Summary

Background:

- CAT-8015 is a modified monoclonal antibody that was designed in the laboratory to target, attack, and destroy specific cancer cells. Researchers are interested in determining the best and safest dose of CAT-8015 to treat patients with specific kinds of lymphoma, such as B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia, that have not responded well to standard treatments or therapies.

Objectives:

- To determine the optimal and maximum tolerated dose of CAT-8015 to treat relapsed or refractory selected types of lymphoma.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, or other selected types of lymphoma, who have not responded well to standard treatments or therapies.

Design:

- Eligible individuals will be asked to provide a blood sample for DNA analysis before receiving CAT-8015.

- Participants will receive intravenous infusions of CAT-8015 in 28-day treatment cycles. Infusions will be given on Days 1, 3, and 5 of each cycle.

- Participants will receive different doses of CAT-8015 depending on when they enter the study, up to a maximum tolerated dose or optimum treatment dose.

- Frequent blood and urine tests will be performed during treatment, as well as other tests as directed by the study doctors. Participants will receive medicines to help prevent possible adverse side effects of CAT-8015, such as allergic reactions or kidney problems.

- At the end of the treatment cycles determined by study doctors, participants will begin a follow-up period with a visit 30 days after the last infusion of CAT-8015, and then every 3 months until the end of the study.

Description

Background:

- HA22 is a recombinant immunotoxin containing an Fv fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin.

- HA22 (CAT-8015) is a mutant form of BL22 which had activity, including complete response (CR), in chemo resistant hairy cell leukemia (HCL) and had activity in chronic lymphocytic leukemia (CLL). HA22 contains 3 amino acids mutations greatly improved binding and cytotoxicity toward CD22+ malignant cells due to lower off-rate, and may enable HA22 to better target the least sensitive CD22+ malignant cells.

Objectives:

- Primary: To determine the maximum tolerated dose (MTD) or optimal biologic dose (OBD) and safety profile of CAT-8015 in subjects with relapsed or refractory advanced B-cell non Hodgkin's lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and CLL (including small lymphocytic lymphoma [SLL]).

The secondary objectives of this study are:

- To describe the preliminary efficacy profile of CAT-8015 in patients with relapsed or refractory advanced B-cell NHL (DLBCL, FL, MCL) or CLL (including small lymphocytic

lymphoma [SLL]).

- Determine pharmacokinetics and immunogenicity of CAT-8015 in subjects with B-cell malignancies and describe the relationship between treatment benefit and safety.

- To determine the % expression of CD22 on tumor lymphocytes in these patient populations and to describe the relationship between treatment benefit and safety.

- To investigate the following clinical and laboratory parameters as potential predictors of vascular leak syndrome (VLS): orthostatic blood pressure, albumin levels, weight changes, edema, and pulmonary findings.

Eligibility

Histologically confirmed B-cell NHL (DLBCL, FL, MCL) and:

- Have relapsed or refractory disease after at least one prior regimen containing rituximab, either alone or in combination.

- Have measurable disease (at least one lesion greater than or equal to 20 mm in one dimension or greater than or equal to 15 mm in two dimensions by conventional or high resolution [spiral] computed tomography (CT).

- Not be a candidate for, or opted not to receive, a hematopoietic stem cell (HSC) or bone marrow (BM) transplant.

OR, confirmation of B-cell CLL (including small lymphocytic lymphoma [SLL]), requiring treatment and:

- Have a characteristic immunophenotype by flow cytometry.

- Have relapsed or refractory disease after at least 2 prior lines of treatment, at least 1 of which must have contained rituximab.

- Not be a candidate for, or opted not to receive, an HSC or BM transplant.

Design (Subjects will be treated on two phases: dose escalation or 4-arm expansion):

Dose Escalation

CAT-8015 will be given as a 30-minute IV infusion at 20, 30, 40, 50, or 60 microg/kg on Days 1, 3, and 5 of every 28-day cycle. Subsequent dose levels with a 10 microg/kg increase from the previous dose level are possible if an MTD or OBD is not reached by 60 microg/kg.

Arm Expansion

In the 4-arm expansion phase, subjects will be treated at the MTD or OBD as identified in the dose-escalation phase.

Study Design

Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Chronic Lymphocytic Leukemia (CLL)

Intervention

CAT-8015

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:15:12-0400

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Medical and Biotech [MESH] Definitions

A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.

A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.

A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.

A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.

A basic helix-loop-helix transcription factor that plays a critical role in HEMATOPOIESIS and as a positive regulator in the differentiation of ERYTHROID CELLS. Chromosome translocations involving the TAL-1 gene are associated with T-CELL ACUTE LYMPHOCYTIC LEUKEMIA.

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