Clinical trial NCT02227108: Study in Pediatrics With Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: B-Cell Pediatric ALL
Keywords: pediatric cancer,pediatric acute lymphoblastic leukemia, lymphoblastic lymphoma, B-cell leukemia, ALL, moxetumomab pasudotox, CD22
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-08-27
Enrollment: 37
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the efficacy of moxetumomab pasudotox in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoblastic lymphoma.

Detailed description: This is a global, multicenter, open-label, single-arm Phase 2 study to evaluate the efficacy and safety of moxetumomab pasudotox monotherapy in pediatric participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Participants will be enrolled at sites in North America, Europe, and Australia. This is an approximate 35 month study.

Eligibility criteria: Inclusion Criteria -

1. Between the ages of greater or equal to (≥) 6 months and less than (\<) 18 years of age
2. Must have histologically proven B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoblastic lymphoma with marrow involvement
3. All participants (both ALL and participants with lymphoblastic lymphoma) must have M2 or M3 bone marrow classification
4. Disease status: a) Participants must have relapsed or refractory disease b) In the event of relapse after prior allogeneic hematopoietic stem cell transplant (HSCT), participants 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 less than or equal to (≤) Grade 2 from prior chemotherapy before entry, in the opinion of the investigator
5. Participants with the following central nervous system (CNS) 1 or 2 status are eligible only in the absence of neurologic symptoms
6. Female participants of childbearing potential and post-pubertal male participants must use an approved method of contraception for the study.

Exclusion Criteria

1. Concurrent enrollment in another clinical study for cancer treatment, unless the subject is in the follow-up period from a previous study.
2. Isolated testicular or CNS ALL
3. Participants with mixed-lineage leukemia (MLL) gene rearrangement
4. Inadequate Hepatic function
5. Inadequate Renal function
6. Radiologically-detected CNS lymphoma
7. Participants with clear laboratory or clinical evidence of disseminated intravascular coagulation (DIC)
8. Hyperleukocytosis or rapidly progressive disease that would compromise ability to complete study therapy
9. QT interval corrected using Fridericia's formula (QTcF) greater than or equal to a Grade 2, confirmed by 2 additional seperate electrocardiographs (ECG's) within 28 days prior to starting study drug. The initial screening ECG need not be repeated for confirmation if the QTcF interval is \<481 milliseconds.
10. Pregnant or breast-feeding females
11. Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox, or any pseudomonas-exotoxin-containing compound
12. 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
13. Systemic chemotherapy ≤ 2 weeks (6 weeks for nitrosoureas) and radiation therapy ≤ 3 weeks prior to starting study drug
14. Clinically significant ophthalmologic findings (evidence of retinal damage or injury) during the screening
15. Presence of a second invasive malignancy
16. Uncontrolled pulmonary infection, presence of pulmonary edema
17. Serum albumin \< 2 gram per deciliter (g/dL). Albumin infusions for correction of hypoalbuminemia are allowed, but cannot have administered within 7 days prior to start of study drug
18. Radioimmunotherapy within 2 years prior to study start of study drug
19. Participants with prior history of thrombotic microangiopathy or hemolytic uremic syndrome (HUS)
20. T-cell ALL or T-cell lymphoblastic lymphoma
21. Participants currently receiving high-dose estrogen therapy defined as \>0.625 milligram per day (mg/day) of an estrogen compound or within 2 weeks prior to starting study drug.

Primary outcomes:
measure: Percentage of Participants With Composite Complete Response (CRc)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
Secondary outcomes:
measure: Percentage of Participants With Minimal Residual Disease (MRD)-Negative CRc Rate
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Overall Response Rate (ORR)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Time to Overall Response
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Best Overall Response (BOR)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Bone Marrow Blast Percentage Change
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Percentage of Participants Who Became Eligible to Receive an Stem Cell Transplant (SCT) After Treatment With Moxetumomab Pasudotox
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Time to Transplant to Receive an Stem Cell Transplant (SCT) After Treatment With Moxetumomab Pasudotox
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Percentage of Participants Who Were Neutropenic at Study Entry and Who Experienced Hematologic Activity (HA)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Duration of Complete Response (DOCR)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Duration of Overall Response (DOR)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Progression-Free Survival (PFS)
timeFrame: Prior to Cycle 1, and prior to every cycle, at the end of treatment, at post-treatment follow-up visits, and at the end of the study, up to 1 year
measure: Overall Survival (OS)
timeFrame: Baseline to end of study or last contact date, up to 1 year
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: Baseline up to 30 days after the last dose of study drug, up to 1 year
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
timeFrame: Baseline up to 30 days after the last dose of study drug, up to 1 year
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Baseline up to 30 days after the last dose of study drug, up to 1 year
measure: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 30 days after the last dose of study drug, up to 1 year
measure: Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
timeFrame: Prior to the Start of Each Cycle for Cycles 1, 2, 3, and Subsequent Odd-Numbered Cycles, End of Treatment, and 30 Day Follow-up Visit, up to 1 year
measure: Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC0-inf) After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion of Day 1 of Cycle 1
measure: Area Under the Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC0-last] After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
measure: Maximum Observed Drug Concentration in Plasma (Cmax) After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
measure: Time to Reach Maximum Drug Concentration in Plasma (Tmax) After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
measure: Terminal Phase Elimination Half Life (t1/2) After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
measure: Systemic Clearance (CL) After the First Dose of Cycle 1
timeFrame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Parkville
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Lyon
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Vandoeuvre les Nancy Cedex
country: France
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: Medimmune Inc. Medimmune Inc.
role: STUDY_DIRECTOR
References:
citation: Mussai F, Campana D, Bhojwani D, Stetler-Stevenson M, Steinberg SM, Wayne AS, Pastan I. Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. Br J Haematol. 2010 Aug;150(3):352-8. doi: 10.1111/j.1365-2141.2010.08251.x. Epub 2010 Jun 7.