A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Participants With Chronic Leukemia

NCT00587457 | Terminated Phase 1 Results

• 1 other identifier: CAT-8015-1002
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 3

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).

Conditions

Leukemia, Lymphoma, Chronic Lymphocytic; Leukemia, Prolymphocytic Leukemia, Small; Lymphocytic Lymphoma, Moxetumomab Pasudotox

Keywords

Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Small Lymphocytic Lymphoma; Moxetumomab pasudotox

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox. Treatment-emergent were events between administration of investigational product and Day 28 that were absent before treatment or that worsened relative to pretreatment state.

  From start of study drug administration until 30 days after the last dose of study drug

• Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)

  The vital sign abnormalities which require an action or intervention by the investigator, or a finding judged by the investigator were reported as an adverse event. TEAEs were events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug.

  From start of study drug administration until 30 days after the last dose of study drug

• Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)

  AEs observed in participants with clinically significant ECG abnormalities were assessed.

  From start of study drug administration until 30 days after the last dose of study drug

• Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)

  An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event. Treatment-emergent were events between first dose of study drug and 30 days after the last dose that were absent before treatment or that worsened relative to pretreatment state. Number of participants with grade 3 or higher treatment-emergent adverse events for laboratory abnormalities were reported as clinically relevant laboratory changes.

  From start of study drug administration until 30 days after the last dose of study drug

• Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)

  Objective response rate defined as the proportion of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria.

  Up to 2 years of post-treatment follow-up

• Best Overall Objective Tumor Response

  Antitumor activity was assessed by best overall objective tumor response.

  Up to 2 years of post-treatment follow-up

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox

  The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.

  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

• Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox

  The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.

  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 (2)

• Number of Participants With Positive Neutralizing Antibodies

  Up to end of treatment (4-6 weeks after the last dose)

• Percentage Change From Baseline in Cluster of Differentiation 22 (CD22) Expression

  End of treatment (4-6 weeks after the last dose)

Study Arms (3)

CAT-8015 5 microgram per kilogram (mcg/kg)

EXPERIMENTAL

Participants received a single intravenous infusion of 5 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

Drug: CAT-8015 5 mcg/kg

CAT-8015 10 mcg/kg

EXPERIMENTAL

Participants received a single intravenous infusion of 10 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

Drug: CAT-8015 10 mcg/kg

CAT-8015 20 mcg/kg

EXPERIMENTAL

Participants received a single intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

Drug: CAT-8015 20 mcg/kg

Interventions

CAT-8015 5 mcg/kg DRUG

Participants received a single intravenous infusion of 5 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

CAT-8015 5 microgram per kilogram (mcg/kg)

CAT-8015 10 mcg/kg DRUG

Participants received a single intravenous infusion of 10 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

CAT-8015 10 mcg/kg

CAT-8015 20 mcg/kg DRUG

Participants received a single intravenous infusion of 20 mcg/kg moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until progressive disease (PD) or until otherwise they become ineligible.

CAT-8015 20 mcg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• History of allogeneic bone marrow transplant.
• 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:

Sponsors & Collaborators

• MedImmune LLC: lead
• Cambridge Antibody Technology: collaborator

Study Sites (3)

Research Site

Indianapolis, Indiana, United States

Location

Research Site

Bethesda, Maryland, United States

Location

Research Site

Lodz, Poland

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Leukemia, Prolymphocytic; Cerebral Palsy; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

immunotoxin HA22

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated early due to unavailability of investigational product.

Results Point of Contact

• Title: Mark C Lanasa
• Organization: MedImmune, LLC.

clinicaltrialenquiries@medimmune.com

301-398-0000

Study Officials

• Mark C Lanasa, M.D.,Ph.D

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 7, 2008
• Study Start: March 7, 2007
• Primary Completion: April 7, 2008
• Study Completion: April 7, 2008
• Last Updated: July 6, 2017
• Results First Posted: April 12, 2017

Record last verified: 2017-06

Locations

PL (1); US (2)