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Phase 3 N=80 Treatment

Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Leukemia, Hairy Cell

Enrolled (actual)
80
Serious AEs
35.0%
Results posted
Aug 2018
Primary outcome: Primary: Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review — 36.3 Percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Moxetumomab pasudotox (Drug); IV Bag Protectant for Moxetumomab pasudotox (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
MedImmune LLC
Primary completion
May 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review
36.3
PRIMARY
Percentage of Participants With Durable CR by Investigator's Assessment
48.8
SECONDARY
Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review
33.8; 7.5
SECONDARY
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment
32.5; 7.5
SECONDARY
Time to CR Assessed by Blinded Independent Central Review
5.9
SECONDARY
Duration of CR Assessed by Blinded Independent Central Review
62.8
SECONDARY
Duration of Hematologic Remission
45.8
SECONDARY
Time to Hematologic Remission
1.1
SECONDARY
Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review
75.0
SECONDARY
Percentage of Participants With Objective Response by Investigator's Assessment
78.8
SECONDARY
Time to Objective Response Assessed by Blinded Independent Central Review
5.7
SECONDARY
Duration of Objective Response Assessed by Blinded Independent Central Review
66.7
SECONDARY
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review
41.5
SECONDARY
Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review
41.5
SECONDARY
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
79; 28
SECONDARY
Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
17; 1; 5; 1; 2; 1
SECONDARY
Number of Participants With Abnormal Vital Signs Reported as TEAEs
9; 3; 12; 6; 25
SECONDARY
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
2; 1; 3; 1; 1; 1
SECONDARY
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox
0.567; 0.550; 0.583
SECONDARY
Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox
192; 435; 379
SECONDARY
Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox
0.841; 3.37; 2.16
SECONDARY
Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox
120; 820; 626
SECONDARY
Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox
869; 856; 1030
SECONDARY
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox
1300; 1470
SECONDARY
Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox
13.2; 14.3; 20.2
SECONDARY
Systemic Clearance (CL) of Moxetumomab Pasudotox
44.6; 31.8
SECONDARY
Terminal Half Life (t1/2) of Moxetumomab Pasudotox
1.38; 1.39
SECONDARY
Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox
87.5; 83.8; 55.2; 98.5

Summary

Background: - Moxetumomab pasudotox is an experimental non-chemotherapy cancer treatment drug. It targets CD22, a molecule on the surface of essentially all hairy cell leukemia cells. Moxetumomab pasudotox binds to CD22, goes into the cell, and releases a toxin which kills the cell. In a phase I trial it had activity in relapsed/refractory hairy cell leukemia with safety profile supporting further clinical study (http://ncbi.nlm.nih.gov/pubmed/22355053). This is a phase III multicenter trial designed to confirm these results.

Eligibility Criteria

  • INCLUSION CRITERIA:
  • Patients must have histologically confirmed hairy cell leukemia or hairy cell leukemia variant .with a need for therapy
  • Patients must be Pseudomonas-immunotoxin naive
  • Patients must have had at least 2 prior purine analogs, or at least 1 course of purine analog and 1 of either rituximab or BRAF inhibitor.
  • Men or women age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 2.
  • Patients must have adequate organ function

EXCLUSION CRITERIA

  • Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study.
  • Patients who are receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial
  • Patients with clinically significant ophthalmologic findings during screening
  • Pregnant or breastfeeding females.
  • Positive for Hepatitis B core antibody or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.
  • Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers
  • HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count of greater than 200.
  • History of allogeneic bone marrow transplant.
  • Patients with history of both thromboembolism and known congenital hypercoagulable conditions.
  • Uncontrolled pulmonary infection, pulmonary edema.
  • Adequate oxygen saturation
  • Radioimmunotherapy within 2 years prior to enrollment in study.
  • Adequate hematologic function
  • Adequate lung function
  • Patients with history of thrombotic microangiopathy or thrombotic microangiopathy / hemolytic uremic syndrome
  • Patients with QTc interval (Friderica) elevation > 500 msec based on at least 2 separate 12-lead ECGs
  • Patient on high dose estrogen
  • Patients with clinical evidence of disseminated intravascular coagulation
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01829711). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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