B-Cell Pediatric ALL Clinical Trial
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
The primary objective of this study is to evaluate the efficacy of moxetumomab pasudotox in pediatric subjects with relapsed or refractory B-cell ALL or B-cell lymphoblastic lymphoma
| Status | Terminated |
| Enrollment | 76 |
| Est. completion date | November 2015 |
| Est. primary completion date | November 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 6 Months to 18 Years |
| Eligibility |
Inclusion Criteria - 1. Between the ages of = 6 months and < 18 years of age 2. Must have histologically proven B-cell ALL or B-cell lymphoblastic lymphoma with marrow involvement. 3. All subjects (both ALL and subjects with lymphoblastic lymphoma) must have M2 or M3 bone marrow classification. 4. Disease status: 1. Subjects must have relapsed or refractory disease 2. 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. 3. Must have resolution of the acute toxic effects to = Grade 2 from prior chemotherapy before entry, in the opinion of the investigator 5. Subjects with the following central nervous system (CNS 1 or 2) status are eligible only in the absence of neurologic symptoms 6. Female subjects of childbearing potential and post-pubertal male subjects 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. Subjects with mixed-lineage leukemia (MLL) gene rearrangement 4. Inadequate Hepatic function 5. Inadequate Renal function 6. Radiologically-detected CNS lymphoma 7. Subjects 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. QTcF interval greater than or equal to a Grade 2, confirmed by 2 additional seperate 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 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. Subject with prior history of thrombotic microangiopathy or HUS. 20. T-cell ALL or T-cell lymphoblastic lymphoma 21. 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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Research Site | Parkville | |
| Australia | Research Site | Westmead | |
| Canada | Research Site | Edmonton | Alberta |
| France | Research Site | Lyon | |
| France | Research Site | Paris | |
| France | Research Site | Vandoeuvre les Nancy Cedex | |
| Italy | Research Site | Rome | |
| Netherlands | Research Site | Rotterdam | |
| Spain | Research Site | Barcelona | |
| Spain | Research Site | Madrid | |
| United Kingdom | Research Site | Bristol | |
| United States | Research Site | Bethesda | Maryland |
| United States | Research Site | Chicago | Illinois |
| United States | Research Site | Columbus | Ohio |
| United States | Research Site | Durham | North Carolina |
| United States | Research Site | Kansas City | Missouri |
| United States | Research Site | Los Angeles | California |
| United States | Research Site | New York | New York |
| United States | Research Site | Philadelphia | Pennsylvania |
| United States | Research Site | Phoenix | Arizona |
| United States | Research Site | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| MedImmune LLC |
United States, Australia, Canada, France, Italy, Netherlands, Spain, United Kingdom,
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Composite complete response (CRc) rate in efficacy evaluable subjects, where CRc is defined as complete response (CR) or CR with incomplete count recovery | Up to 34 months | No | |
| Secondary | Measure for the number and pecentage of subjects with serious adverse events (SAE's) | Evaluated using routine safety tests | Up to 34 Months | Yes |
| Secondary | Assessment of pharmacokinetics (AUC, Cmax, clearance, half-life) of moxetumomab pasudotox | Will evaluate PK parameters | Up to 34 Months | No |
| Secondary | Efficacy of moxetumomab pasudotox measured by: Minimal residual disease (MRD)-negative CRc rate | Up to 34 Months | No | |
| Secondary | Efficacy of moxetumomab pasudotox measured by the proportion of evaluable subjects who become eligible to receive a stem cell transplant (SCT) | Up to 34 Months | No | |
| Secondary | Efficacy of moxetumomab pasudotox measured by the proportion of subjects who are neutropenic at study entry and who experience hematologic activity | Up to 34 Months | No | |
| Secondary | 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) | Up to 34 Months | No | |
| Secondary | Number and percentage of subjects who develop detectable anti-drug antibodies and neutralizing antibodies | Number of subjects who develop anti-drug antibodies | Up to 34 Months | No |
| Secondary | Efficacy of moxetumomab pasudotox measured by: overall response rate (ORR) | Up to 34 Months | No | |
| Secondary | Efficacy of moxetumomab pasudotox measured by time to transplant for evaluable subjects who become eligible to receive a SCT | Up to 34 Months | No | |
| Secondary | number and percentage of subjects with adverse events (AEs). | Evaluated using routine safety tests | Up to 34 Months | Yes |