A Phase I, Multicenter Dose Escalation Study in Patients With Hairy Cell Leukemia

MedImmune

Status and phase: Completed; Phase 1

Conditions: Hairy Cell Leukemia

Treatments: Drug: Moxetumomab Pasudotox (CAT 8015); Drug: CAT 8015 (Moxetumomab Pasudotox)

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00586924

CAT-8015-1001

Details and patient eligibility

About

A dose-escalation study to identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), defined as the highest dose that can safely be given to a participant and establish the safest dose based on the highest tolerated dose for clinical testing.

Full description

A Phase 1, multicenter, dose escalation study of moxetumomab pasudotox (CAT-8015) in participants with relapsed or refractory hairy cell leukemia (HCL) to estimate the MTD, defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on the MTD, for subsequent clinical testing (Phase 2 recommended dose).

Enrollment: 49 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Confirmed diagnosis of HCL, Measurable disease, Participant's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted less than (<) 2 years, or if the participant had unacceptable toxicity to purine analog, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, Participant's with other cancers who meet eligibility criteria and have less than 5 years of disease free survival will be considered on a case-by-case basis, Life expectancy of greater than 6 months, as assessed by principal investigator, Must be able to understand and sign informed consent, Must be at least 18 years old, Female and male participants must agree to use an approved method of contraception during the study.

Exclusion Criteria: - History of allogeneic bone marrow transplant, Documented and ongoing central nervous system involvement with their malignant disease (history of central nervous system (CNS) involvement is not an exclusion criteria), Pregnant or breast-feeding females, HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs, Hepatitis B surface antigen positive. - Hepatic function: Serum transaminases (either alanine transaminase (ALT) or aspartate transaminase (AST)) or bilirubin: greater than or equal to (>=) Grade 2, unless bilirubin is due to Gilbert's disease. -Renal function: Serum creatinine clearance less than or equal to (<=) 60 millilitre per minute (mL/min) as estimated by Cockroft-Gault formula. -Hematologic function: The absolute neutrophil count (ANC) < 1000/ cubic millimetres (cmm), or platelet count <50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy). -Pulmonary function: Participant's with < 50% of predicted forced expiratory volume (FEV1) or <50% of predicted diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration and alveolar volume. Uncontrolled pulmonary infection, presence of pulmonary edema, Oxygen saturation at rest < 88% measured by pulse oximetry or partial pressure of oxygen (PaO2) < 55 millimetre(s) of mercury (mm Hg), Serum albumin < 2 g/dL, Radioimmunotherapy within 2 years prior to enrollment in study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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49 participants in 6 patient groups

5 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 5 microgram per kilogram (mcg/kg) moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

10 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

20 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

30 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

40 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: CAT 8015 (Moxetumomab Pasudotox)

50 mcg/kg

Experimental group

Description:

Participants received intravenous infusion of 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Treatment:

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)

Drug: Moxetumomab Pasudotox (CAT 8015)