A Phase 1-2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
| Status: | Archived |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | February 2010 |
| End Date: | April 2013 |
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.
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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