A Phase 2, Multicenter, Single-arm Study of Moxetumomab Pasudotox in Pediatric Subjects with Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma of B-cell Origin

Subjects must meet all of the following criteria:
1. Between the ages of >= 6 months and < 18 years of age at the time of screening
2. Written informed consent and written informed assent (if applicable) and any locally required authorization (eg, HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
3. Must have histologically proven B-cell ALL or B-cell lymphoblastic lymphoma with marrow involvement according to the French-American-British classification. NOTE: Subjects with extramedullary involvement outside of the CNS will not be excluded provided they have 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 and have received at least one standard chemotherapy and either one salvage regimen or allogeneic stem cell transplant.
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 Principal Investigator or designee
6. For non-leukemic subjects (ie, subjects with lymphoma), an ANC > 1,000/µL and platelet count > 50,000/mm2 are required, unless cytopenias are judged by the Principal Investigator or designee to be due to underlying disease (ie, potentially reversible with antineoplastic therapy). NOTE: There will be no WBC count, ANC, hemoglobin (Hgb), or platelet count requirement for enrollment of subjects with leukemia.
7. Performance status:
* For subjects >= 12 years of age, Eastern Cooperative Oncology Group (ECOG) score <= 2 (Appendix 2)
* For subjects < 12 years of age, Lansky scale >= 50% (Appendix 3)
* Subjects who are unable to walk, but who are upright in a wheel chair will be considered ambulatory (ECOG score >= 1 and <= 2, Lansky score >= 50% and <= 70%) for the purpose of calculating performance status (a conversion chart from ECOG, Karnofsky, and Lansky is located in Appendix 4).
8. Subjects with the following CNS status (CNS 1 or 2 as described below) are eligible only in the absence of neurologic symptoms, such as cranial nerve palsy, suggestive of CNS leukemia:
a. CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs
b. CNS 2, defined as presence of < 5/µL WBCs in CSF and cytospin positive for blasts, or > 5/µL WBCs but negative by the Steinherz/Bleyer algorithm:
i. CNS 2a: < 10/µL red blood cells (RBCs); < 5/µL WBCs and cytospin positive for blasts
ii. CNS 2b: >= 10/µL RBCs; < 5/µL WBCs and cytospin positive for blasts
iii. CNS 2c: >= 10/µL RBCs; >= 5/µL WBCs and cytospin positive for blasts, but negative by Steinherz/Bleyer algorithm (Appendix 1).
9. With permission from the parents/legal guardian, as required by local regulations, study staff will discuss with female subjects of childbearing potential and post-pubertal male subjects the use of an approved method of contraception for the study. Sexually active subjects must agree to use an approved method of contraception (see Table 4.2.1-1) or to abstain from vaginal sexual intercourse from screening through 90 days after the last dose of investigational product.;Table 4.2.1-1 Highly Effective Methods of Contraception
Barrier Methods:
Male condom plus spermicide
Copper T intrauterine device
Levonorgesterel-releasing intrauterine system
(eg. Mirena®)
This is also considered a hormonal method ;Hormonal Methods:
Implants
Hormone shot or injection
Combined pill
Mini pill
Patch

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) 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.