A Clinical Trial of Investigational Agent (Moxetumomab Pasudotox) in Patients with Relapsed/ Refractory Hairy Cell Leukemia

Phase 1

Conditions: Hairy Cell Leukemia
MedDRA version: 21.0Level: LLTClassification code 10019056Term: Hairy cell leukemia variantSystem Organ Class: 100000004864
MedDRA version: 21.0Level: LLTClassification code 10019055Term: Hairy cell leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003233-26-IT

Lead Sponsor: MEDIMMUNE, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

Inclusion Criteria

Patients must have histologically confirmed hairy cell leukemia or hairy
cell leukemia variant .with a need for therapy based on at least one of
the following criteria:
neutrophils less than 1000/mm(3)
platelets less than 100,000/mm(3)
hemoglobin less than 10 g/dL)
symptomatic splenomegaly.
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 rituximub or BRAF inhibitor.
Men or women age greater than or equal to 18 years. Because this
disease does not generally occur in children, children are excluded from
this study, but will be eligible for future pediatric trials in other indications.
ECOG performance status less than or equal to 2.
The effects of moxetumomab pasudotox on the developing human fetus
are unknown. For this reason, women of child-bearing potential and men
must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry and for the duration of
study participation, and 4 months after completion of moxetumomab
pasudotox administration. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study,
she should inform her treating physician immediately.
Patients must have adequate organ function as defined below:
total bilirubin less than or equal to 1.5 mg/dL, unless consistent with
Gilbert s (ratio between total and direct bilirubin greater than 5)
AST and ALT less than or equal to 3 times upper limit of normal (ULN)
alkaline phosphatase less than or equal to 2.5 ULN
serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance
greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault
equation
Prothrombin time/INR or partial thromboplastin time less 2.5 ULN,
fibrinogen greater than or equal to 0.5 LLN; if on warfarin, INR less than
3.5, if on any other anticoagulation, PT less than 2.5 times baseline
Ability to understand and the willingness to sign a written informed
consent document.
Life expectancy greater than or equal to 6 months
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

Patients who have had chemotherapy, immunotherapy or radiotherapy
within 4 weeks prior to initiation of treatment.
Patients who are receiving any other investigational agents.
Patients with known brain metastases should be excluded from this
clinical trial because of their poor prognosis and because they often
develop progressive neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events.
Patients with clinically significant ophthalmologic findings during
screening
Pregnant or breastfeeding females. The effects of moxetumomab
pasudotox on the developing fetus are unknown. Because there is an
unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with moxetumomab pasudotox
breastfeeding should be discontinued if the mother is treated with
moxetumomab pasudotox
Positive for Hepatitis B 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
Uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, malaria infection or psychiatric
illness/social situations that would limit compliance with study
requirements.
HIV-positive patients unless taking appropriate anti-HIV medications
with a CD4 count of greater than 200. Otherwise, there may be increased
risk of lethal infections when temporarily suppressing normal B-cells.
History of allogeneic bone marrow transplant.
Patients with history of both thromboembolism and known congenital
hypercoagulable conditions.
Uncontrolled pulmonary infection, pulmonary edema. Oxygen saturation at rest less than 88% measured by pulse oximetry or
PaO (2) less than or equal to 55 mm Hg.
Serum albumin less than 2 g/dL.
Radioimmunotherapy within 2 years prior to enrollment in study.
ANC less than 1000/mm(3), or platelet count less than 50,000/mm(3),
if these cytopenias are not judged by the investigator to be due to
underlying disease (ie, potentially reversible with antineoplastic
therapy). A patient 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.
Patients with less than 50% of predicted forced expiratory volume
(FEV1) or less than 50% of predicted diffusing capacity for carbon
monoxide (DLCO), corrected for hemoglobin concentration and alveolar
volume. Note: Patients with no prior history of pulmonary illness are not
required to have PFTs. FEV1 will be assessed after bronchodilator
therapy.
Patients with history of thrombotic microangiopathy or TTP-HUS.
Patients with QTc elevation > grade 1
Patient on high dose estrogen (defined as > 0.625 mg/day of an
estrogen compound.
Patients with clinical evidence of disseminated intravascular coagulation (grade 3-4)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the rate of durable complete response (CR) in multiply relapsed HCL with moxetumomab pasudotox.;Secondary Objective: Determine the overall response rate (ORR), progression-free survival<br>(PFS), time to treatment failure (TTF), and duration of responses (CR<br>and partial response [PR]).<br>-Confirm the tolerability and safety of moxetumomab pasudotox in<br>patients with HCL.<br>-Evaluate immunogenicity and pharmacokinetics (PK) of moxetumomab pasudotox.;Primary end point(s): Durable Complete response;Timepoint(s) of evaluation of this end point: Approximately 12 months from the start of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Overall Response Rate (ORR), progression free survival (PFS), time to<br>treatment failute, duration fo response (CR and PR), Safety,Immunogenicty, and Pharmokokinetics;Timepoint(s) of evaluation of this end point: Duration of study

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