Clinical trial NCT00586924: A Phase I, Multicenter Dose Escalation Study in Patients With Hairy Cell Leukemia
Official title: A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Hairy Cell Leukemia (HCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hairy Cell Leukemia
Keywords: CAT-8015
Moxetumomab pasudotox
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
Collaborators: name: Cambridge Antibody Technology
First posted: 2008-01-07
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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).

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days)
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 (approximately 8 years)
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 (approximately 8 years)
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 (approximately 8 years)
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 (approximately 8 years)
measure: Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Number of Participants With Complete Response (CR)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Number of Participants With Partial Response (PR)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Number of Participants With Stable Disease (SD)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Number of Participants With Progressive Disease (PD)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Time to Complete Response
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Time to Objective Response
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Duration of Complete Response
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Duration of Objective Response
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Time to Progression
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Progression-free Survival (PFS)
timeFrame: From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1
timeFrame: Cycle 1 Day 1: pre-infusion; at 15 minutes (min) during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 hours (h) post infusion
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5
timeFrame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1
timeFrame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5
timeFrame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1
timeFrame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5
timeFrame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1
timeFrame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5
timeFrame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1
timeFrame: Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5
timeFrame: Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
timeFrame: Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion
measure: Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
timeFrame: Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion
Secondary outcomes:
measure: Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity
timeFrame: Up to end of treatment (approximately 8 years)
measure: CD22 Expression Levels From Peripheral Blood by Best Response
timeFrame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
measure: CD22 Expression Levels From Bone Marrow by Best Response
timeFrame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
measure: Soluble CD22 Levels by Best Response
timeFrame: Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Lodz
country: Poland
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References:
citation: Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, Fitzgerald DJ, Lechleider R, Pastan I. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1822-8. doi: 10.1200/JCO.2011.38.1756. Epub 2012 Feb 21.
citation: Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, FitzGerald DJ, Santiago L, Gao G, Lanasa MC, Pastan I. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood. 2018 May 24;131(21):2331-2334. doi: 10.1182/blood-2017-09-803072. Epub 2018 Feb 27.