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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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 Lympho

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 Summary: 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.
Sponsor: MedImmune LLC

Current Primary Outcome: 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.


Original Primary Outcome: Composite complete response (CRc) rate in efficacy evaluable subjects, where CRc is defined as complete response (CR) or CR with incomplete count recovery [ Time Frame: Up to 34 months ]

Current Secondary Outcome:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Duration of Complete Response (DOCR) [ Time Fram

    Original Secondary Outcome:

    • Measure for the number and pecentage of subjects with adverse events (AE's) [ Time Frame: Up to 34 Months ]
      Evaluated using routine safety tests
    • Assessment of pharmacokinetics (AUC, Cmax, clearance, half-life) of moxetumomab pasudotox [ Time Frame: Up to 34 Months ]
      Will evaluate PK parameters
    • Efficacy of moxetumomab pasudotox measured by: Minimal residual disease (MRD)-negative CRc rate [ Time Frame: Up to 34 Months ]
    • Efficacy of moxetumomab pasudotox measured by the proportion of evaluable subjects who become eligible to receive a stem cell transplant (SCT) [ Time Frame: Up to 34 Months ]
    • Efficacy of moxetumomab pasudotox measured by the proportion of subjects who are neutropenic at study entry and who experience hematologic activity [ Time Frame: Up to 34 Months ]
    • Efficacy of moxetumomab pasudotox measured by the duration of complete response (DOCR), duration of overall response (DOR), progression-free survival (PFS), and overall survival (OS) [ Time Frame: Up to 34 Months ]
    • Measure for the number and percentage of subjects with serious adverse events (SAE's) [ Time Frame: Up to 34 Months ]
    • Number and percentage of subjects who develop detectable anti-drug antibodies and neutralizing antibodies [ Time Frame: Up to 34 Months ]
      Number of subjects who develop anti-drug antibodies
    • Efficacy of moxetumomab pasudotox measured by: overall response rate (ORR) [ Time Frame: Up to 34 Months ]
    • Efficacy of moxetumomab pasudotox measured by time to transplant for evaluable subjects who become eligible to receive a SCT [ Time Frame: Up to 34 Months ]


    Information By: MedImmune LLC

    Dates:
    Date Received: August 21, 2014
    Date Started: August 2014
    Date Completion:
    Last Updated: March 9, 2017
    Last Verified: March 2017