Phase 1
Completed N=55
CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
Source: ClinicalTrials.gov NCT00659425 ↗Enrolled (actual)
55
Serious AEs
67.3%
Results posted
Oct 2017
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 0; 0; 2 participants
Summary
A dose-escalation study to estimate maximum cummulative dose (MTCD) of CAT-8015 that can be safely administered to a participant.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 0; 0; 2; 0; 1 | — |
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
1; 1; 1; 4; 4; 5 | — |
| PRIMARY Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) |
0; 0; 0; 2; 3; 3 | — |
| PRIMARY Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) |
0; 1; 1; 1; 2; 1 | — |
| PRIMARY Treatment-Emergent Adverse Events (TEAEs) Related to Chemistry Abnormalities Occurring in Greater Than (>) 5 Percent of Participants |
0; 1; 0; 2; 0; 4 | — |
| PRIMARY Number of Participants With Abnormalities in Ophthalmologic Examination at End of Treatment That Were Not Present at Baseline |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Normal Sinus Rhythm Findings in ECG |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline to End of Treatment in Clinical Findings in Electrocardiogram (ECG) QT, QTC Interval and Ventricular Rate |
-107; NA; NA; NA; -52.0; NA | — |
| PRIMARY Best Overall Tumor Response |
0; 1; 0; 1; 0; 1 | — |
| PRIMARY Objective Response Rate (ORR) |
0; 100; 0; 25.0; 0; 50.0 | — |
| PRIMARY Percentage of Participants With Relapse of Disease |
0; 100; 0; 0; 0; 50 | — |
| PRIMARY Time to Disease Response |
0.69; 0.49; 0.66; 0.49; 0.72; 0.62 | — |
| PRIMARY Duration of Response (DR) |
NA; 2.3; NA; NA; NA; NA | — |
| PRIMARY Time to Disease Progression (TDP) |
0.2; NA; NA; 2; NA; NA | — |
| PRIMARY Progression-Free Survival (PFS) |
0.2; 3.6; 1.7; 1.8; NA; 3.1 | — |
| PRIMARY Overall Survival (OS) |
0.2; 3.6; 1.7; 2.1; NA; 4.6 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox |
NA; 126; 274; 446; 446; 555 | — |
| PRIMARY Area Under the Serum Concentration Time Curve From Time Zero to Infinity (AUC [0 to Infinity]) for Moxetumomab Pasudotox |
NA; NA; 744; 1060; 844; 1320 | — |
| PRIMARY Systemic Clearance (CL) for Moxetumomab Pasudotox |
NA; NA; 40.5; 35.4; 47.5; 34.6 | — |
| PRIMARY Terminal Phase Elimination Half Life (t1/2) for Moxetumomab Pasudotox |
NA; NA; 0.906; 1.32; 0.997; 0.880 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibody |
0; 0; 0; 1; 1; 1 | — |
| SECONDARY CD22 Expression Cells in Peripheral Blood by Best Response |
NA; 14519.0; NA; 749.0; NA; 3058.0 | — |
| SECONDARY Number of Participants With Potential Biomarkers of Predicting Capillary Leak Syndrome (CLS) |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed diagnosis of acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma; - Measurable or evaluable disease. - Evidence of CD22-positive malignancy by one of the following criteria: - greater than or equal to (>=) 30 % of malignant cells from a disease site cluster of differentiation 22+ (CD22+) by fluorescence-activated cell sorter (FACS) analysis or; ≥ 15 % of malignant cells from a disease site CD22+ by immunohistochemistry (IHC). Stage of disease: - Participants must have relapsed or refractory disease and have received at least one standard chemotherapy and one salvage regimen or allogeneic stem cell transplant; - Relapse after prior autologous or allogeneic HSCT is allowed. In the event of relapse after prior allogeneic HSCT, the participant must be at least 100 days post-transplant and have no evidence of ongoing active graft-vs-host disease; - Recovered from the acute toxic effects of all prior therapy before entry. Performance status: - Participants greater than or equal to (>=) 12 years of age: Eastern Cooperative Oncology Group (ECOG) score of 0, 1, 2, or 3; - Participants = 50%; - Participants who are unable to walk because of paralysis, but who are up in a wheel chair will be considered ambulatory for the purpose of calculating the performance score. Participants with the following central nervous system (CNS) status, are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy. - Female and male participants with childbearing potential and their sexual partners must agree to use an approved method of contraception during the study.
Exclusion Criteria
- Participants meeting any of the following criteria are not eligible for participation in the study: - Isolated testicular or CNS ALL; Hepatic function: - Inadequate liver function defined as total bilirubin > 2 × upper limit of normal (ULN) (except in the case of participants with documented Gilbert's disease > 5 × ULN) or transaminases (ALT and aspartate aminotransferase [AST]) > 5 × ULN based on age- and laboratory-specific normal ranges; Renal function: - With greater than age-adjusted normal serum creatinine (see Table below) and a creatinine clearance > 60 millilitre per minute mL/min/1.73 m2. - Age(Years)- Maximum Serum Creatinine (mg/dl)[≤5,0.8] [5 15, 1.5] Hematologic function: - For non-leukemic subjects only, absolute neutrophil count (ANC) < 1000/cmm, or platelet count < 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (ie potentially reversible with anti-neoplastic therapy); - Participants with CNS 3 disease; - Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease (PD) that in the estimation of the investigator and sponsor would compromise ability to complete study therapy; - Prior treatment with CAT-3888 (BL22) or any pseudomonas-exotoxin-containing compound; - HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs); - Active hepatitis B or C infection.
Data sourced from ClinicalTrials.gov (NCT00659425). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.