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) of B-cell Origin
MedDRA version: 18.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-003101-10-DE

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
Subjects must meet all of the following criteria:
1) Between the ages of = 6 months and < 18 years of age
2) Written informed consent and written informed assent (if applicable)
3) Must have histologically proven B-cell ALL with marrow involvement
4) Measurable or evaluable disease
5) Disease status:
• Subjects must have relapsed or refractory disease and received at least 1 standard chemotherapy and either 1 salvage regimen or allogeneic HSCT.
• In event of relapse after prior allogeneic HSCT, subjects must be at least 3 months post-transplant, have no evidence of active graft-vs-host disease, and been off immunosuppression for at least 4 weeks
• 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) status 1 or 2 are eligible only in the absence of neurologic symptoms, such as cranial nerve palsy, suggestive of CNS leukemia.
8) Female subjects of childbearing potential and post-pubertal male
subjects must agree to use an approved method of contraception for the study (if sexually active) or abstinence to meet eligibility criteria.
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
Any of the following would exclude the subject from participation in the study:
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, unless it is a non-interventional, observational study or the subject is in the follow-up period from a previous study, or prior sponsor approval is obtained
3) Employees of the study site directly involved with the conduct of the study at the site of proposed enrollment, or immediate family members of any such individuals
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) Laboratory findings or clinical evidence consistent with Grade = 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct
10) Hyperleukocytosis (WBC = 50,000/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
11) Pregnant or breast-feeding females
12) A QTcF interval (manually overread) of = 481 msec (ie, = Grade 2) confirmed by medically qualified staff on at least 2 separate electrocardiograms (ECGs) performed at least 5 min apart within 28 days prior to enrollment
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 enrollment, 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) Other investigational antineoplastic agents within 30 days prior to Cycle 1, Dose of study treatment
17) Seropositivity for Human immunodeficiency virus (HIV)
18) Seropositivity for hepatitis B (HBsAg) or hepatitis C (HCV antibody)
19) Clinically significant ophthalmologic findings (evidence of retinal damage or injury) during the screening
20) 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
21) Presence of a second invasive malignancy
22) Any physical, social, or psychiatric condition, or any other condition which in the opinion of the principal investigator or designee would prevent effective study cooperation or participation in the study
23) Uncontrolled pulmonary infection, presence of pulmonary edema
24) Inadequate oxygen saturation
25) Serum albumin < 2 g/dL
26) Radioimmunotherapy within 2 years prior to enrollment in study
27) Subject with prior history of thrombotic microangiopathy or HUS.
28) Previous life-threatening anaphylactic reactions to prior monoclonal antibody-based immunotherapy or any component of the moxetumomab pasudotox formulation
29) T-cell ALL or T-cell lymphoblastic lymphoma
30) History of known congenital hypercoaguable condition
31) Subjects receiving high-dose estrogen therapy
32) For German Investigative Sites: Subjects with B-cell lymphoblastic lymphoma will be excluded.

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

Related Trials