Clinical trial NCT00587457: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Participants With Chronic Leukemia
Official title: A Phase I, Multicenter, Dose-Escalation Study of CAT-8015 in Patients With Relapsed or Refactory Chronic Lymphocytic Leukemia (CLL) Prolymphocytic Leukemia (PLL), or Small Lymphocytic Leukemia (SLL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Lymphoma, Chronic Lymphocytic
Leukemia, Prolymphocytic Leukemia, Small
Lymphocytic Lymphoma, Moxetumomab Pasudotox
Keywords: Chronic Lymphocytic Leukemia
Prolymphocytic Leukemia
Small Lymphocytic Lymphoma
Moxetumomab pasudotox
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Cambridge Antibody Technology
First posted: 2008-01-07
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of moxetumomab pasudotox in relapsed or refractory participants with chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL) or Small Lymphocytic Lymphoma (SLL).

Detailed description: This was a multicenter, Phase 1, standard 3+3 dose-escalation study to evaluate the safety and anti-neoplastic activity of CAT-8015 in relapsed or refractory participants with CLL, PLL, or SLL. Participants in the initial dose cohort were to receive CAT-8015 at a dose of 5 microgram per kilogram (mcg/kg) CAT-8015, increasing to 10 mcg/kg in the second dose cohort, and then increasing by 10 mcg/kg increments in subsequent cohorts (that is, to doses of 20, 30, 40, 50, 60 mcg/kg, etc) until a maximum tolerated dose (MTD) was identified. Following identification of the MTD, the MTD cohort was to be expanded to 16 participants.

Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of B-Cell Leukemia \[(chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), or Small lymphocytic leukemia (SLL)\]
* Measurable Disease
* Disease characteristics: Participants with CLL or SLL are eligible if they have failed 2 or more prior courses of standard chemo and/or biologic therapy (example, Rituxan) and PLL will be eligible if they have failed at least one prior standard chemotherapeutic regimen. Medical indications for treatment include progressive disease-related symptoms, progressive cytopenias due to marrow involvement, progressive or painful splenomegaly or adenopathy, rapidly increasing lymphocytosis, autoimmune hemolytic anemia or thrombocytopenia and increased frequency of infections.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Participants with other cancers who meet eligibility criteria and have had 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 the principal investigator
* Must be able to understand and sign the informed consent
* Must be at least 18 years old
* Female and Male participants 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 \[history of central nervous system (CNS) involvement is not an exclusion criterion\]
* Pregnant or breast-feeding females
* Participants who plasma contains either a significant level of antibody to CAT-8015 as measured by ELISA, or antibody that neutralizes the binding of CAT-8015 to CD22 as measured by a competition ELISA.
* HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs)
* Hepatitis B surface antigen positive
* Uncontrolled, symptomatic, intercurrent illness including but not limited to: infections requiring systemic antibiotics, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
* Hepatic function: Serum transaminases \[either alanine aminotransferase (ALT) or aspartate aminotransferase (AST)\] or direct bilirubin greater than or equal to Grade 2, unless bilirubin is due to Gilbert's disease
* Renal function: Serum creatinine clearance is less than or equal to 60 millilitre per minute (mL/min) as estimated by Cockcroft-Gault formula

Hematologic function:

* The ANC less than 1000/cubic millimeter (cmm), or platelet count less than 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (that is, potentially reversible with anti-neoplastic therapy).
* A participant will not be excluded because of pancytopenia greater than or equal to Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies.
* Baseline coagulopathy greater than or equal to grade 3 unless due to anticoagulant therapy

Pulmonary function:

- Participants with less than 50 percent (%) of predicted forced expiratory volume (FEV-1) or less than 50% of predicted diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin concentration and alveolar volume. Note: Participants with no prior history of pulmonary illness are not required to have pulmonary function test (PFTs). FEV1 will be assessed after bronchodilator therapy.

Recent prior therapy:

* Cytotoxic chemotherapy, corticosteroids (except stable doses of prednisone), whole body electron beam radiation therapy, hormonal, biologic or other standard or any investigational therapy of the malignancy for 3 weeks prior to entry into the trial.
* Less than or equal to 1 month prior monoclonal antibody therapy (that is, rituximab)
* Participants who are receiving or have received radiation therapy less than 3 weeks prior to study entry will not be excluded providing the volume of the bone marrow treated is less than 10% and also the participant has measurable disease outside the radiation report.
* Any history of prior pseudomonas - exotoxin immunotoxin administrator

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration until 30 days after the last dose of study drug
measure: Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)
timeFrame: Up to 2 years of post-treatment follow-up
measure: Best Overall Objective Tumor Response
timeFrame: Up to 2 years of post-treatment follow-up
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox
timeFrame: Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
measure: Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox
timeFrame: Predose, 0.25 (During Infusion), 0.5 (End of Infusion), 1, 1.5, 2, 4, 8 and 12 hours postdose on Day 1 and 5; Predose and End of Infusion on Day 3
Secondary outcomes:
measure: Number of Participants With Positive Neutralizing Antibodies
timeFrame: Up to end of treatment (4-6 weeks after the last dose)
measure: Percentage Change From Baseline in Cluster of Differentiation 22 (CD22) Expression
timeFrame: End of treatment (4-6 weeks after the last dose)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Lodz
country: Poland
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Mark C Lanasa, M.D.,Ph.D
role: STUDY_DIRECTOR
References: