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: 100000004864
MedDRA version: 20.0 Level: LLT Classification code 10019056 Term: Hairy cell leukemia variant System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003233-26-IE

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:
i) neutrophils less than 1000/mm(3)
ii) platelets less than 100,000/mm(3)
iii) haemoglobin less than 10 g/dL
iv) symptomatic splenomegaly.
2. Patients must be Pseudomonas-immunotoxin naive
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 greater than or equal to 18 years. Because this disease does not generally occur in children, children are excluded from this study.
5. ECOG performance status less than or equal to 2.
6. Patients must have adequate organ function as defined below:
i) 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)
ii) AST and ALT less than or equal to 3 times upper limit of normal (ULN)
iii) alkaline phosphatase less than or equal to 2.5 ULN
iv) 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
7. 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
8. Ability to understand and the willingness to sign a written informed consent document.
9. Life expectancy greater than or equal to 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.
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
F.1.3.1 Number of subjects for this age range 7

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.
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 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
6. 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.
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, cardiac arrhythmia, malaria infection or psychiatric illness/social situations that would limit compliance with study requirements.
9. Known 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.
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 less than 88% measured by pulse oximetry or PaO(2) less than or equal to 55 mm Hg.
14. Serum albumin less than 2 g/dL.
15. Radioimmunotherapy within 2 years prior to enrollment in study.
16. 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.
17. 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.
18. Patients with history of thrombotic microangiopathy or TTP-HUS.
19. Patients with QTc elevation > grade 1
20. Patient on high dose estrogen (defined as > 0.625 mg/day of an estrogen compound.
21. Patients with clinical evidence of disseminated intravascular c

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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