A Phase 2, Multicenter Study in Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma

Conditions: Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma of B-cell Origin
MedDRA version: 18.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
MedDRA version: 18.0Level: LLTClassification code 10003939Term: B-lymphoblastic lymphoma (Kiel Classification)System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-003101-10-NL

Lead Sponsor: MedImmune, LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 76

Inclusion Criteria

Inclusion Criteria -
1) Between the ages of = 6 months and < 18 years of age
2) Written informed consent and written informed assent
3) Must have histologically proven B-cell ALL or B-cell lymphoblastic lymphoma with marrow involvement.
4) All subjects (both ALL and subjects with lymphoblastic lymphoma) must have M2 or M3 bone marrow classification.
5) Disease status:
a) Subjects must have relapsed or refractory disease
b) In the event of relapse after prior allogeneic HSCT, subjects must be at least 3 months post-transplant and have no evidence of active graft-vs-host disease, and must have been off immunosuppression for at least 4 weeks.
c) Must have resolution of the acute toxic effects to = Grade 2 from prior chemotherapy before entry, in the opinion of the investigator
6) Adequate Performance status.
7) Subjects with the following central nervous system (CNS 1 or 2) status are eligible only in the absence of neurologic symptoms
8) Female subjects of childbearing potential and post-pubertal male subjects must use an approved method of contraception for the study
Are the trial subjects under 18? yes
Number of subjects for this age range: 76
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria
1) Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
2) Concurrent enrollment in another clinical study for cancer treatment, unless the subject is in the follow-up period from a previous study.
3) Employees of the study site directly involved with the conduct of the study at the site of proposed enrollment, or an immediate family member of any such individual
4) Isolated testicular or CNS ALL
5) Subjects with mixed-lineage leukemia (MLL) gene rearrangement
6) Inadequate Hepatic function
7) Inadequate Renal function
8) Radiologically-detected CNS lymphoma
9) Subjects with clear laboratory or clinical evidence of disseminated intravascular coagulation (DIC)
10) Hyperleukocytosis or rapidly progressive disease that would compromise ability to complete study therapy
11) A QTcF interval (manually overread) of = 481 milliseconds (ie, = Grade 2) that is confirmed by 2 additional separate electrocardiograms (ECGs) within 28 days prior to starting study drug. The initial screening ECG need not be repeated for confirmation if the QTcF interval (manual overread) is < 481 milliseconds.
12) Pregnant or breast-feeding females
13) Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox, or any pseudomonas-exotoxin-containing compound
14) Prior treatment with any anticancer biologic therapy within 2 weeks prior to starting study drug , including but not limited to therapeutic monoclonal antibodies or antibody-drug conjugates.
15) Systemic chemotherapy = 2 weeks (6 weeks for nitrosoureas) and radiation therapy = 3 weeks prior to starting study drug with exceptions per protocol
16) Seropositivity for human immunodeficiency virus (HIV)
17) Seropositivity for hepatitis B (HBsAg) or hepatitis C (HCV antibody)
18) Clinically significant ophthalmologic findings (evidence of retinal damage or injury) during the screening
19) Uncontrolled, symptomatic, intercurrent illness including, but not limited to infection, congestive heart failure, cardiac arrhythmia, malaria infection or any other condition that would limit compliance with study requirements
20) Presence of a second invasive malignancy.
21)Any physical, social, or psychiatric condition, or any other condition which in the opinion of the Principal Investigator or designee would prevent effective cooperation or participation in the study
22) Uncontrolled pulmonary infection, presence of pulmonary edema
23) Inadequate Oxygen saturation
24) Serum albumin < 2 g/dL. Albumin infusions for correction of hypoalbuminemia are allowed, but cannot have been administered within 7 days prior to start of study drug.
25) Radioimmunotherapy within 2 years prior to start of study drug.
26) Subject with prior history of thrombotic microangiopathy or HUS.
27) T-cell ALL or T-cell lymphoblastic lymphoma
28) History of known congenital hypercoaguable condition
29) Previous life-threatening anaphylactic reactions to prior monoclonal antibody-based immunotherapy or any component of the moxetumomab pasudotox formulation
30) Subjects currently receiving high-dose estrogen therapy defined as >0.625mg/day of an estrogen compound or within 2 weeks prior to starting study drug.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Assess the efficacy defined as Composite Complete Response (CRc);Secondary Objective: • Assess safety and tolerability<br>• Assess immunogenicity and pharmacokinetics<br>• Progression-free survival (PFS), overall survival (OS), Duration of complete response (DOCR), Duration of overall response (DOR)<br>• Minimal residual disease negative CRc rate<br>• Number eligible for stem cell transplant<br>• Overall response rate (ORR)<br>• Hematologic activity;Primary end point(s): Assess the efficacy defined as composite complete response (CRc);Timepoint(s) of evaluation of this end point: Disease assessments will be completed prior to the first cycle and subsequent cycles

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Assess safety and tolerability<br>• Assess immunogenicity and pharmacokinetics<br>• PFS, OS, DOCR, DOR<br>• Minimal residual disease negative CRc rate<br>• Number eligible for stem cell transplant<br>• ORR<br>• Hematologic activity;Timepoint(s) of evaluation of this end point: Duration of study

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