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NCT00586924

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

Completed Phase 1 Results posted Last updated 2 April 2019
What this trial tests

Phase 1 trial testing Moxetumomab Pasudotox (CAT 8015) in Hairy Cell Leukemia in 49 participants. Completed in 6 May 2015.

Timeline
10 May 2007
Primary endpoint
6 May 2015
6 May 2015

Quick facts

Lead sponsorMedImmune LLC
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment49
Start date10 May 2007
Primary completion6 May 2015
Estimated completion6 May 2015
Sites4 locations across United States, Poland

Drugs / interventions tested

Conditions studied

Sponsor

MedImmune LLC — full company profile →

Who can join

Adults 18 to 99, any sex, with Hairy Cell Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days)

Adverse events are suspected of causal relationship to drug and are \>=Grade (G) 3 in severity considered DLTs: G 3 or 4 hematologic abnormalities at baseline due to disease were not evaluable for hematologic DLT, G 2 allergic reactions of bronchospasm or urticaria, or any \>= G3 allergic reaction, in presence of pre-medication were considered DLTs. Following \>= G 3 non-hematological treatment-related toxicities not considered DLTs: Tumor lysis syndrome, G 3 low electrolyte levels with pre-existing low levels of same electrolytes, anticoagulant therapy, G 3 or 4 infection or neutropenic fever

GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg0
40 mcg/kg0
50 mcg/kg0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) Primary · From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

The TEAEs are defined as adverse events (AEs) 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 d

TEAEs
GroupValue95% CI
5 mcg/kg3
10 mcg/kg3
20 mcg/kg3
30 mcg/kg3
40 mcg/kg4
50 mcg/kg33
TESAEs
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg2
40 mcg/kg0
50 mcg/kg4
Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) Primary · From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Vital signs abnormalities reported as TEAEs included pyrexia, weight increased, dyspnoea, hypoxia, hypertension, hypotension.

Pyrexia
GroupValue95% CI
5 mcg/kg1
10 mcg/kg1
20 mcg/kg2
30 mcg/kg3
40 mcg/kg1
50 mcg/kg16
Weight increased
GroupValue95% CI
5 mcg/kg1
10 mcg/kg0
20 mcg/kg0
30 mcg/kg0
40 mcg/kg0
50 mcg/kg6
Dyspnoea
GroupValue95% CI
5 mcg/kg1
10 mcg/kg0
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg6
Hypoxia
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg1
Hypertension
GroupValue95% CI
5 mcg/kg0
10 mcg/kg1
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg0
Hypotension
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg2
40 mcg/kg0
50 mcg/kg10
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) Primary · From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Cardiac AEs observed in participants with clinically significant ECG abnormalities included; ECG QT prolonged, Sinus tachycardia and Atrioventricular block first degree.

ECG QT prolonged
GroupValue95% CI
5 mcg/kg1
10 mcg/kg0
20 mcg/kg0
30 mcg/kg2
40 mcg/kg0
50 mcg/kg2
Sinus tachycardia
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg2
Atrioventricular block first degree
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg0
40 mcg/kg1
50 mcg/kg0
Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) Primary · From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

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.

Alanine aminotransferase increased
GroupValue95% CI
5 mcg/kg1
10 mcg/kg1
20 mcg/kg1
30 mcg/kg3
40 mcg/kg2
50 mcg/kg25
Aspartate aminotransferase increased
GroupValue95% CI
5 mcg/kg2
10 mcg/kg1
20 mcg/kg1
30 mcg/kg2
40 mcg/kg1
50 mcg/kg24
Blood alkaline phosphatase increased
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg5
Blood bicarbonate decreased
GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg0
40 mcg/kg0
50 mcg/kg5
Blood bilirubin increased
GroupValue95% CI
5 mcg/kg2
10 mcg/kg1
20 mcg/kg1
30 mcg/kg0
40 mcg/kg1
50 mcg/kg2
Blood creatine phosphokinase increased
GroupValue95% CI
5 mcg/kg0
10 mcg/kg1
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg4
Blood creatinine increased
GroupValue95% CI
5 mcg/kg1
10 mcg/kg0
20 mcg/kg0
30 mcg/kg1
40 mcg/kg0
50 mcg/kg11
Blood triglycerides increased
GroupValue95% CI
5 mcg/kg0
10 mcg/kg1
20 mcg/kg0
30 mcg/kg1
40 mcg/kg1
50 mcg/kg2
Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) Primary · 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)

Objective response rate defined as proportion of participants with confirmed CR or confirmed PR according to Response Evaluation Criteria for hairy cell leukemia (HCL). A CR is defined as: No evidence of leukemic cells by routine H/E stains of peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as: Neutrophils \>= 1,500/mcL, Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gm/dL without transfusions or growth factors for at least 4 weeks. Partial response requires a

GroupValue95% CI
5 mcg/kg3
10 mcg/kg3
20 mcg/kg2
30 mcg/kg2
40 mcg/kg3
50 mcg/kg29
Number of Participants With Complete Response (CR) Primary · 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)

The CR is defined by: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as exhibited by: Neutrophils \>= 1,500/microliter (mcL), Platelets \>= 100,000/mcL, and Hemoglobin \>= 11.0 gram per deciliter (gm/dL) without transfusions or growth factors for at least 4 weeks.

GroupValue95% CI
5 mcg/kg0
10 mcg/kg2
20 mcg/kg2
30 mcg/kg1
40 mcg/kg2
50 mcg/kg21
Number of Participants With Partial Response (PR) Primary · 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)

Partial response requires all of the following: \>=50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, \>=50% reduction in lymphadenopathy, \>=50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam, Neutrophils \>= 1,500/mcL or 50% improvement over baseline without growth factors for at least 4 weeks, Platelets \>=100,000/mcL or 50% improvement over baseline, and Hemoglobin \>= 11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. For participants who are transfusion-dependent at

GroupValue95% CI
5 mcg/kg3
10 mcg/kg1
20 mcg/kg0
30 mcg/kg1
40 mcg/kg1
50 mcg/kg8
Number of Participants With Stable Disease (SD) Primary · 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)

Stable disease was characterized by not meeting the criteria for CR, PR or PD.

GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg1
30 mcg/kg1
40 mcg/kg0
50 mcg/kg4
Number of Participants With Progressive Disease (PD) Primary · 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)

Progressive disease is defined by at least one of the following compared to pretreatment:\>= 25% increase in the sum of the products of the greatest perpendicular dimensions of at least two lymph nodes on two consecutive examinations at least 2 weeks apart (at least 1 node must be \>= 2 cm) or appearance of new palpable lymph nodes, \>=25% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, or appearance of new palpable hepatomegaly or splenomegaly that was not previously present, \>=50% increase in the absolute number of circulating

GroupValue95% CI
5 mcg/kg0
10 mcg/kg0
20 mcg/kg0
30 mcg/kg0
40 mcg/kg1
50 mcg/kg0
Time to Complete Response Primary · 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)

Time to complete response (CR) was measured from the start of moxetumomab pasudotox treatment to the first documentation of CR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved a CR. Time to complete response was summarized using Kaplan-Meier estimates (median time, 95% confidence interval \[CI\] for median time).

GroupValue95% CI
10 mcg/kg2.532.30 – 2.76
20 mcg/kg9.564.11 – 15.01
30 mcg/kg3.713.71 – 3.71
40 mcg/kg2.532.27 – 2.79
50 mcg/kg3.942.30 – 6.31
Time to Objective Response Primary · 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)

Time to OR was measured from the start of moxetumomab pasudotox treatment to the first documentation of OR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved an OR (CR or PR). Objective response (OR) was defined as the participants with confirmed CR or confirmed PR according to Response Evaluation Criteria.

GroupValue95% CI
5 mcg/kg3.022.04 – 4.80
10 mcg/kg1.120.92 – 2.76
20 mcg/kg8.21.38 – 15.01
30 mcg/kg8.181.87 – 14.49
40 mcg/kg1.080.95 – 2.79
50 mcg/kg1.050.92 – 1.58

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

5 mcg/kg
Serious: 0/3 (0%)
Deaths:
10 mcg/kg
Serious: 0/3 (0%)
Deaths:
20 mcg/kg
Serious: 0/3 (0%)
Deaths:
30 mcg/kg
Serious: 2/3 (67%)
Deaths:
40 mcg/kg
Serious: 0/4 (0%)
Deaths:
50 mcg/kg
Serious: 4/33 (12%)
Deaths:

Serious adverse events (9 terms)

ReactionSystem5 mcg/kg10 mcg/kg20 mcg/kg30 mcg/kg40 mcg/kg50 mcg/kg
Febrile neutropeniaBlood and lymphatic system disorders
Haemolytic uraemic syndromeBlood and lymphatic system disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
Blood creatinine increasedInvestigations
BronchospasmRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Other adverse events (76 terms — click to expand)

ReactionSystem5 mcg/kg10 mcg/kg20 mcg/kg30 mcg/kg40 mcg/kg50 mcg/kg
LymphopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
HypertriglyceridaemiaMetabolism and nutrition disorders
White blood cell count decreasedInvestigations
PyrexiaGeneral disorders
NauseaGastrointestinal disorders
Oedema peripheralGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
HypermagnesaemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
ChillsGeneral disorders
Blood creatinine increasedInvestigations
Neutrophil count decreasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Haemoglobin decreasedInvestigations
HypercholesterolaemiaMetabolism and nutrition disorders
ProteinuriaRenal and urinary disorders
FatigueGeneral disorders
OedemaGeneral disorders
DizzinessNervous system disorders
Haemorrhage urinary tractRenal and urinary disorders
RashSkin and subcutaneous tissue disorders
RhinitisInfections and infestations
Gamma-glutamyltransferase increasedInvestigations
Haptoglobin decreasedInvestigations
HypomagnesaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Capillary leak syndromeVascular disorders
Platelet count decreasedInvestigations
Weight increasedInvestigations
HypernatraemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders

Most-reported serious reactions: Febrile neutropenia, Haemolytic uraemic syndrome, Pyrexia, Pneumonia, Blood creatinine increased, Bronchospasm, Dyspnoea, Hypoxia.

Data from ClinicalTrials.gov NCT00586924 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A guide to taming a toxin--recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer.
    Weldon JE, Pastan I. · · 2011 · cited 183× · PMID 21585657 · DOI 10.1111/j.1742-4658.2011.08182.x
  2. Moxetumomab Pasudotox: First Global Approval.
    Dhillon S. · · 2018 · cited 117× · PMID 30357593 · DOI 10.1007/s40265-018-1000-9
  3. Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up.
    Kreitman RJ, Tallman MS, Robak T, Coutre S, et al · · 2018 · cited 55× · PMID 29487070 · DOI 10.1182/blood-2017-09-803072
  4. <i>Pseudomonas</i> Exotoxin-Based Immunotoxins: Over Three Decades of Efforts on Targeting Cancer Cells With the Toxin.
    Havaei SM, Aucoin MG, Jahanian-Najafabadi A. · · 2021 · cited 49× · PMID 34976821 · DOI 10.3389/fonc.2021.781800
  5. Linked-in: design and efficacy of antibody drug conjugates in oncology.
    Feld J, Barta SK, Schinke C, Braunschweig I, et al · · 2013 · cited 29× · PMID 23651630 · DOI 10.18632/oncotarget.924
  6. Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia.
    Kuruvilla D, Chia YL, Balic K, Yao NS, et al · · 2020 · cited 10× · PMID 32077130 · DOI 10.1111/bcp.14250
  7. Clinically approved immunotoxins targeting hematological cancers: "the best of both worlds".
    Rashad Y, Alt EU, Izadpanah R, Qin X, et al · · 2025 · cited 1× · PMID 41181593 · DOI 10.3389/fphar.2025.1569502
  8. Aberrant glycosylation in hematologic malignancies: mechanisms, immune evasion, and therapeutic targeting.
    Lu X, Song Z, Wang C, Pan B, et al · · 2026 · PMID 41963305 · DOI 10.1038/s41408-026-01493-z

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