E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A specific type of cancer of the blood |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019055 |
E.1.2 | Term | Hairy cell leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019056 |
E.1.2 | Term | Hairy cell leukemia variant |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the rate of durable complete response (CR) in multiply relapsed HCL with moxetumomab pasudotox. |
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E.2.2 | Secondary objectives of the trial |
-Determine the overall response rate (ORR), progression-free survival (PFS), time to treatment failure (TTF), and duration of responses (CR and partial response [PR]).
-Confirm the tolerability and safety of moxetumomab pasudotox in patients with HCL.
-Evaluate immunogenicity and pharmacokinetics (PK) of moxetumomab pasudotox. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Durable Complete response |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 12 months from the start of treatment |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Belgium |
Brazil |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Mexico |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |