NCT00659425

A Phase 1, Multicenter, Dose Escalation Study of CAT-8015 in Children, Adolescents and Young Adults With Refractory CD22+ Acute Lymphoblastic Leukemia (ALL) or Non-Hodgkin Lymphoma (NHL)

Completed Phase 1 Results posted Last updated 28 August 2017

What this trial tests

Phase 1 trial testing CAT-8015 (Moxetumomab Pasudotox) in Acute Lymphoblastic Leukemia in 57 participants. Completed in 1 December 2014.

Timeline

1 September 2008

Primary endpoint
1 December 2014

1 December 2014

Quick facts

Lead sponsor	MedImmune LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	57
Start date	1 September 2008
Primary completion	1 December 2014
Estimated completion	1 December 2014
Sites	5 locations across United States, Canada

Drugs / interventions tested

• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)
• CAT-8015 (Moxetumomab Pasudotox)

Conditions studied

• Acute Lymphoblastic Leukemia — all drugs for Acute Lymphoblastic Leukemia →
• Non-Hodgkin's Lymphoma — all drugs for Non-Hodgkin's Lymphoma →

Sponsor

MedImmune LLC — full company profile →

Who can join

Adults 6 Months to 25, any sex, with Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of Participants With Dose Limiting Toxicities (DLTs)
  Time frame: Day 1 up to 21 days of Cycle 1 (each cycle duration was of 21 days)
  Adverse events that were suspected of a relationship to moxetumomab pasudotox and were greater than or equal to (\>=) Grade 3 in severity were considered DLTs with the following additional criteria or exceptions: Participants with hematologic abnormalities of any grade, Grade 2 allergic reactions of bronchospasm or urticaria, or any Grade ≥ 3 allergic reaction, in the presence of premedication.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
  Time frame: From start of study drug administration until 30 days after the last dose of study drug
  An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant
• Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
  Time frame: From start of study drug administration until 30 days after the last dose of study drug
  Vital signs included parameters as heart rate, blood pressure, temperature, weight, pulse oximetry and respiratory rate. 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.
• Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
  Time frame: From start of study drug administration up to 30 days after the last dose of study drug
  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
• Treatment-Emergent Adverse Events (TEAEs) Related to Chemistry Abnormalities Occurring in Greater Than (>) 5 Percent of Participants
  Time frame: From start of study drug administration up to 30 days after the last dose of study drug
  An abnormal chemistry 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 p
• Number of Participants With Abnormalities in Ophthalmologic Examination at End of Treatment That Were Not Present at Baseline
  Time frame: Baseline and end of treatment (up to 1 year after the last participants begins study drug treatment)
  Ophthalmologic examination included evaluation of retinal, corneal and lens abnormalities at baseline and end of treatment that were not present at screening. Participants who experienced abnormalitities during ophthalmologic examination recorded and reported.

Sponsor's own description

A dose-escalation study to estimate maximum cummulative dose (MTCD) of CAT-8015 that can be safely administered to a participant.

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. Immunotoxins for leukemia.
   Wayne AS, Fitzgerald DJ, Kreitman RJ, Pastan I. · · 2014 · cited 82× · PMID 24578503 · DOI 10.1182/blood-2014-01-492256
3. Evolution of <i>Escherichia coli</i> Expression System in Producing Antibody Recombinant Fragments.
   Sandomenico A, Sivaccumar JP, Ruvo M. · · 2020 · cited 70× · PMID 32878291 · DOI 10.3390/ijms21176324
4. Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia.
   Mussai F, Campana D, Bhojwani D, Stetler-Stevenson M, et al · · 2010 · cited 58× · PMID 20528877 · DOI 10.1111/j.1365-2141.2010.08251.x
5. Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia.
   Wayne AS, Shah NN, Bhojwani D, Silverman LB, et al · · 2017 · cited 56× · PMID 28983018 · DOI 10.1182/blood-2017-02-749101
6. <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
7. Immunotoxin resistance via reversible methylation of the DPH4 promoter is a unique survival strategy.
   Wei H, Xiang L, Wayne AS, Chertov O, et al · · 2012 · cited 43× · PMID 22509046 · DOI 10.1073/pnas.1204523109
8. Novel agents for the treatment of childhood acute leukemia.
   Annesley CE, Brown P. · · 2015 · cited 41× · PMID 25830014 · DOI 10.1177/2040620714565963