Study in Pediatrics With Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma

March 9, 2017 updated by: MedImmune LLC

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Parkville, Australia
        • Research Site
      • Westmead, Australia
        • Research Site
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
        • Research Site
  • France
      • Lyon, France
        • Research Site
      • Paris, France
        • Research Site
      • Vandoeuvre les Nancy Cedex, France
        • Research Site
  • Italy
      • Rome, Italy
        • Research Site
  • Netherlands
      • Rotterdam, Netherlands
        • Research Site
  • Spain
      • Barcelona, Spain
        • Research Site
      • Madrid, Spain
        • Research Site
  • United Kingdom
      • Bristol, United Kingdom
        • Research Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States
        • Research Site
    • California
      • Los Angeles, California, United States
        • Research Site
    • Illinois
      • Chicago, Illinois, United States
        • Research Site
    • Maryland
      • Bethesda, Maryland, United States
        • Research Site
    • Missouri
      • Kansas City, Missouri, United States
        • Research Site
    • New York
      • New York, New York, United States
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States
        • Research Site
    • Ohio
      • Columbus, Ohio, United States
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Research Site
    • Washington
      • Seattle, Washington, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Moxetumomab Pasudotox 40 mcg/kg
Participants received 6 doses of moxetumomab pasudotox 40 microgram per kilogram (mcg/kg) intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Drug: Moxetumomab Pasudotox
Participants received 6 doses of moxetumomab pasudotox 40 microgram per kilogram (mcg/kg) intravenous infusion over 30 minutes every other day (Days 1, 3, 5, 7, 9, and 11) in 21-day treatment cycles until completion of a maximum of 6 cycles of therapy.
Other Names:
  • CAT-8015

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Composite Complete Response (CRc)
Time Frame: 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
The CRc is defined as achieving complete response (CR), or CR with incomplete count recovery [CRi]) in participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts. The efficacy assessments were evaluated as per investigator assessment.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Minimal Residual Disease (MRD)-Negative CRc Rate
Time Frame: 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
The MRD-negative CRc rate was defined as the percentage of participants who achieved CRc and became MRD-negative as determined by flow cytometry performed by a central analysis laboratory. The CRc is defined as complete response (CR), or complete response with incomplete count recovery (CRi). Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts.
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
Overall Response Rate (ORR)
Time Frame: 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
The ORR, defined as the percentage of participants with CRc or partial response (PR), was estimated; the Clopper Pearson (Exact) 95% CI was calculated. The CRc is defined as complete response (CR), or complete response with incomplete count recovery (CRi). Complete response (CR) as per International Working Group (IWG) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Morphologic CR with incomplete blood count recovery (CRi) is defined as the above CR criteria without specified blood counts.
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
Time to Overall Response
Time Frame: 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
Time to overall response was evaluated using the Kaplan-Meier method.
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
Best Overall Response (BOR)
Time Frame: 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
The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number and percentage of participants for the following categories: CRc, PR, HA, SD, PD, and not evaluable. Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes and in size of liver or spleen. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD.
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
Bone Marrow Blast Percentage Change
Time Frame: 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
Change in bone marrow blast percentage from baseline was evaluated. If the percentage (%) blasts (at least 200 cells counted) is less than (<) 5%, it is considered as M1, 5 to 25% considered as M2, greater than (>) 25% considered as M3. Stages with the higher blasts relate to worse outcomes.
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
Percentage of Participants Who Became Eligible to Receive an Stem Cell Transplant (SCT) After Treatment With Moxetumomab Pasudotox
Time Frame: 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
The percentage of participants who became eligible for SCT after treatment with moxetumomab pasudotox were provided. The Clopper Pearson (Exact) 95% CI was calculated.
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
Time to Transplant to Receive an Stem Cell Transplant (SCT) After Treatment With Moxetumomab Pasudotox
Time Frame: 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
The time to SCT was defined as the duration from the start of treatment with moxetumomab pasudotox until the date when the subject became eligible for SCT. The time to SCT was to be summarized using the Kaplan-Meier method, and was only to be evaluated for the subgroup of subjects who became eligible for SCT after treatment with moxetumomab pasudotox.
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
Percentage of Participants Who Were Neutropenic at Study Entry and Who Experienced Hematologic Activity (HA)
Time Frame: 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
The percentage of participants who were neutropenic at study entry and experienced HA after treatment with moxetumomab pasudotox was evaluated. The Clopper Pearson (Exact) 95% CI was calculated.
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
Duration of Complete Response (DOCR)
Time Frame: 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
DOCR was defined as the duration from the first documentation of CRc to the first documented disease progression.The CRc is defined as achieving complete response (CR), or CR with incomplete count recovery [CRi]) in participants with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma. Kaplan-Meier method was used for evaluation.
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
Duration of Overall Response (DOR)
Time Frame: 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
DOR was to be defined as the duration from the first documentation of overall response to the first documented disease progression. Kaplan-Meier method was used for evaluation.
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
Progression-Free Survival (PFS)
Time Frame: 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
PFS was measured from the start of treatment with moxetumomab pasudotox until the first documentation of disease progression or death due to any cause, whichever occurred first. Kaplan-Meier method was used for evaluation.
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
Overall Survival (OS)
Time Frame: Baseline to end of study or last contact date, up to 1 year
OS was determined as the time from the start of treatment with moxetumomab pasudotox until death due to any cause. For participants who were alive at the end of the study or lost to follow-up, OS was censored on the last date when the participant was known be alive. Kaplan-Meier method was used for evaluation.
Baseline to end of study or last contact date, up to 1 year
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 1 year
Treatment-emergent adverse events (TEAEs), were defined as events present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug.
Baseline up to 30 days after the last dose of study drug, up to 1 year
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAE)
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 1 year
Laboratory tests were grouped according to hematology, serum chemistry, and urinalysis. Laboratory abnormalities with toxicity grades according to NCI CTCAE Version 4.03 were derived according to laboratory values and reported as treatment-emergent adverse events.
Baseline up to 30 days after the last dose of study drug, up to 1 year
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 1 year
Participants were evaluated for ECG abnormalities.
Baseline up to 30 days after the last dose of study drug, up to 1 year
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 1 year
Participants who experienced vital signs abnormalities recorded as TEAEs were reported.
Baseline up to 30 days after the last dose of study drug, up to 1 year
Number of Participants With Positive Anti-drug Antibody (ADA) and Neutralizing Antibodies (NAb)
Time Frame: 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
Immunogenicity assessment included determination of antidrug (moxetumomab pasudotox) antibodies and neutralizing antidrug antibodies in serum samples. Titers and specificity were determined for NAb-positive participants. Specificity were observed in participants who had ADAs directed to the PE38 domain of moxetumomab pasudotox and increase in titers were observed in participants who tested ADA-positive at baseline. Moxetumomab pasudotox ADA-titer is a validated immunoassay, which determines titers or levels of ADAs present in ADA-positive samples.
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
Area Under the Plasma Concentration Time Curve From Time 0 to Infinity (AUC0-inf) After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion of Day 1 of Cycle 1
AUC (0-infinity) = Area under the serum concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (tinfinity). It was calculated by extrapolating the concentrationtime curve from time zero to infinity using the linear/log trapezoidal rule.
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion of Day 1 of Cycle 1
Area Under the Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration [AUC0-last] After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample. AUC0-t is defined as AUC from time zero to the last data point above the lower limit of quantification.
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Maximum Observed Drug Concentration in Plasma (Cmax) After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Time to Reach Maximum Drug Concentration in Plasma (Tmax) After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Terminal Phase Elimination Half Life (t1/2) After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Terminal phase elimination half-life is the time measured for the serum/plasma concentration to decrease by one half, calculated as natural logarithmic (log)-transformed (ln) value of 2 divided by elimination rate constant (lambda); that is [ln(2)/lambda]. Elimination rate constant (lambda) was estimated via linear regression of the time versus log concentration.
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
Systemic Clearance (CL) After the First Dose of Cycle 1
Time Frame: Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]).
Pre-infusion, end of infusion (EOI); 1, 3, and 6 hours post-infusion at Day 1 of Cycle 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MedImmune LLC

Investigators

  • Study Director: Medimmune Inc. Medimmune Inc., MedImmune LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

August 21, 2014

First Submitted That Met QC Criteria

August 25, 2014

First Posted (Estimate)

August 27, 2014

Study Record Updates

Last Update Posted (Actual)

April 6, 2017

Last Update Submitted That Met QC Criteria

March 9, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CD-ON-CAT-8015-1036

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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