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

Phase 1

Conditions: Hairy Cell Leukemia
MedDRA version: 20.0 Level: LLT Classification code 10019055 Term: Hairy cell leukemia System Organ Class: 100000012994
MedDRA version: 20.0 Level: LLT Classification code 10019056 Term: Hairy cell leukemia variant System Organ Class: 100000012994
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003233-26-PL

Lead Sponsor: MedImmune, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 77

Inclusion Criteria

1. 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:
a. neutrophils < 1.0x 10(9)/L
b. platelets < 100 x 10(9)/L
c. hemoglobin < 10 g/dL
d. symptomatic splenomegaly
2. Patients must be Pseudomonas-immunotoxin naïve
3. Patients must have received at least 2 prior systemic therapies, including 2 courses of courses of a PNA, or 1 course of either rituximab or BRAF inhibitor following a single prior course of PNA.
4. Men or women age = 18 years. Because this disease does not generally occur in children, children are excluded from this study.
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2
6. Patients must have adequate organ function as defined below:
a. total bilirubin = 1.5 mg/dL, unless consistent with Gilbert’s (ratio between total and direct bilirubin > 5)
b. AST and ALT = 3x upper limit of normal (ULN)
c. alkaline phosphatase = 2.5 ULN
d. serum creatinine = 1.5 mg/dL or creatinine clearance = 60 mL/min as estimated by the Cockcroft-Gault equation
7. Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) < 2.5 ULN, fibrinogen = 0.5 lower limit of normal; if on warfarin, INR < 3.5, if on any other anticoagulation, PT < 2.5 x baseline
8. Ability to understand and the willingness to sign a written informed consent document.
9. Life expectancy = 6 months.
10. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception prior to study entry and or the duration of study participation, and must agree to continue using such precautions for 4 months after completion of moxetumomab pasudotox administration; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
? Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are premenarchal or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
? A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly.
? 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.
11. Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 for 60 days after receipt of the final dose of investigational product.
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

Exclusion Criteria

1. Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to initiation of treatment.
2. Patients who are receiving any other investigational agents.
3. 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 (AEs).
4. Patients with retinal or choroidal detachment identified during the screening ophthalmologic evaluation.
5. Pregnant or breastfeeding females. The effects of moxetumomab pasudotox on the developing fetus are unknown. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with moxetumomab pasudotox breastfeeding should be discontinued if the mother is treated with moxetumomab pasudotox.
6. Positive for Hepatitis B core antibody or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral DNA load is < 2000 IU/mL.
7. Active second malignancy requiring treatment other than minor resection of indolent cancers like basal cell and squamous skin cancers.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled hypertension, cardiac arrhythmia, malaria infection, or psychiatric illness/social situations that would limit compliance with study requirements.
9. Known human immunodeficiency virus (HIV)-positive patients unless taking appropriate anti-HIV medications with a CD4 count of > 200. Otherwise, there may be increased risk of lethal infections when temporarily suppressing normal B-cells.
10. History of allogeneic bone marrow transplant.
11. Patients with history of both thromboembolism and known congenital hypercoagulable conditions.
12. Uncontrolled pulmonary infection, pulmonary edema
13. Oxygen saturation at rest < 88% measured by pulse oximetry or PaO2 = 55 mm Hg
14. Serum albumin < 2 g/dL
15. Radioimmunotherapy within 2 years prior to enrollment in the study.
16. Absolute neutrophil count (ANC) < 1.0 x 10(9)/L, or platelet count < 50 x 10(9)/L, unless judged by the investigator to be due to underlying disease (ie, potentially reversible with anti-neoplastic therapy). A patient will not be excluded because of pancytopenia = Grade 3, or erythropoietin dependence, if due to disease, based on the results of bone marrow studies.
17. Patients with < 50% of predicted forced expiratory volume (FEV1) or < 50% of predicted diffusing capacity for carbon monoxide, corrected for hemoglobin concentration and alveolar volume (DLCO). Note: Patients with no prior history of pulmonary illness are not required to have pulmonary function testing (PFT). Forced expiratory volume will be assessed after bronchodilator therapy.
18. Patients with history of thrombotic microangiopathy or thrombotic microangiopathy / HUS.
19. Patients with corrected QT interval (Frederica) elevation > 500 msec (manually over-read by medically qualified person) based on at least two separate 12-lead ECGs.

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.;<br> Secondary Objective: -Determine the overall response rate (ORR), progression-free survival (PFS), time to treatment failure (TTF), and duration of responses (CR and partial response [PR]).<br> -Confirm the tolerability and safety of moxetumomab pasudotox in patients with HCL.<br> -Evaluate immunogenicity and pharmacokinetics (PK) of moxetumomab pasudotox.<br> ;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 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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