A Phase 1 Study of Every Other Week XmAb®2513 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Patients With Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma
A Phase 1 Study of Every Other Week XmAb®2513 to Evaluate the Safety, Tolerability, and
Pharmacokinetics in Patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma
An open-label, multi-dose, single-arm, Phase 1 dose escalation study of XmAb2513 will be
conducted to define the maximum tolerated dose (MTD) or recommended dose(s) for further
study, to determine safety and tolerability, to characterize PK and immunogenicity, and to
evaluate antitumor activity of XmAb2513 in patients with HL and ALCL (non-cutaneous) and who
have received two or more prior therapeutic regimens. There will be no intra-patient dose
The trial target Patients who are > 18 years old with a histological diagnosis of Hodgkin
Lymphoma (HL) or Anaplastic Large Cell Lymphoma (ALCL [non-cutaneous] ) and who have
received two or more prior therapeutic regimens, one of which should include hematopoietic
cell transplant, either autologous or allogeneic transplant.
Treatment is given every 2 weeks for 4 doses. Patients with complete response (CR), partial
response (PR) or stable disease (SD) may continue until progressive disease (PD) or a max of
8 doses. All patients will complete 3 months of follow-up or up to next treatment.
Administration of XmAb2513 (0.3, 1.0, 3.0, 6.0, 9.0 , 12.0 mg/kg) IV over 2 hours. Initial
dosing will occur using an accelerated dose escalation design. Dose escalation will be
divided into two segments: the initial accelerated escalation phase and the standard
escalation phase. During the initial accelerated dose escalation phase, dose escalation may
occur after treatment of one patient per cohort provided that there is no DLT and no Grade 2
or greater, treatment-related toxicity. Treatment-related is defined as probably or
possibly related to study drug. The dose escalation safety assessment period will include
data from the first 4 weeks of treatment (2 doses or one cycle).
At the point that a patient experiences a treatment-related DLT or treatment-related, Grade
2 or greater toxicity (based on the NCI CTCAE version 3) during the dose escalation safety
assessment period, the initial accelerated escalation phase will end, the standard dose
escalation phase will begin, and the cohort in which the event occurred will be expanded to
a total of 3 patients (2 additional patients will be enrolled).
From this point forward the standard 3+3 dose escalation rules will apply (the standard
escalation phase). If none of 3 patients have a DLT then dose escalation to the next level
will occur. If 1 of the 3 patients experiences a DLT, then the cohort will be further
expanded to 6 patients (3 additional patients will be enrolled). If there are no additional
patients with a DLT, dose escalation to the next higher dose level will occur. During the
dose escalation period, any cohort with 2 or more patients experiencing a DLT will have
exceeded the MTD and there will be no further dose escalation.
Safety/tolerability will be assessed by Physical examination, clinical laboratory tests
[hematology and blood chemistry, urinalysis, PT/PTT, international normalized ratio (INR)]
HAHA, cytokine levels, vital signs, and toxicity assessment.
Clinical disease activity: CT of neck, chest, pelvis and abdomen will be performed at the
completion of 8 weeks of therapy, CT/PET will be performed at weeks 8 and 16.
FDG PET scanning will be used to monitor anti-CD30 metabolic effects and incorporated into
Blood samples will be analyzed for serum levels of XmAb2513 and soluble CD30. Human anti-
XmAb2513 antibodies will also be monitored.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Identification of the maximum tolerated dose and identification of the recommended dose of XmAb®2513 for evaluation in future studies.
Anas Younes, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Rush University Medical Center||Chicago, Illinois 60612-3824|
|Ohio State University||Columbus, Ohio 43210|