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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


Phase 1
18 Years
N/A
Not Enrolling
Both
Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma

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Trial Information

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
escalation.

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
response criteria.

Blood samples will be analyzed for serum levels of XmAb2513 and soluble CD30. Human anti-
XmAb2513 antibodies will also be monitored.


Inclusion Criteria:



- Diagnosed with HL or ALCL.

- Patients must provide tumor tissue for confirmation of histologic diagnosis and
presence of CD30 in the tumor tissue. Archived paraffin embedded samples are
acceptable for patients who have no prior exposure to another anti-CD30 therapy and
samples should be provided from the most recent biopsy and if possible from the
original biopsy as well. Patients who have previously received anti-CD30 regimens
must also have a biopsy performed and assessed for CD30 expression prior to study
enrollment to confirm the presence of CD30 in the tumor tissue. The biopsy may be
performed during the screening period or may have been performed after progression
from the last anti-tumor therapy was completed.

- Patients must have received two or more prior therapeutic regimens, one of which
should include hematopoietic cell transplant, either autologous or allogeneic
transplant.

- If a hematopoietic cell transplant was refused, or the patient was not eligible to
receive a transplant, the patient is still eligible to participate in the trial if
the patient has received two or more prior chemotherapy based regimens.

- Patients who have received allogeneic transplant must not have relapsed less than 6
months after their transplant and they must be at least 200 days post-transplant
prior to enrollment. Additionally, there must be no evidence of GVHD and the patient
must be stable without immunosuppressive treatment, including systemic
corticosteroids (per os [po] or iv), for > 3 months prior to enrollment.

- Patients who have previously received any targeted anti-CD30 therapies are eligible
provided that the therapy was completed at least 6 months prior to enrollment, there
is no residual toxicity, and there is evidence of CD30 positivity on recent or new
biopsy. Additionally, these patients must be negative for anti-XmAb2513 antibodies.

- Patients should have at least one radiographically measurable site of disease of 1.5
cm in the largest dimension.

- Patients must have completed all anti-cancer treatment > 4 weeks prior to enrollment.
Patients who have received a hematopoietic cell transplant must have completed
immunosuppressive treatment, including systemic corticosteroids for > 3 months prior
to enrollment.

- Patients must have completed any palliative corticosteroid therapy (e.g. for
management of Type B symptoms) > 2 weeks prior to enrollment.

- Patients must have received two or more prior therapeutic regimens, one of which
should include hematopoietic cell transplant, either autologous or allogeneic
transplant.

- Patients must be 18 years of age.

- Required baseline laboratory data:

- Platelet count 80,000/mm3 (patients must not be platelet transfusion-dependent
as evidenced by maintenance of platelet count above 50,000/mm3 in the 28 days
prior to enrollment without transfusion)

- Absolute neutrophil count > 1,500/mm3

- Creatinine ≤ 1.5 times ULN

- ALT (SGPT) /AST (SGOT) ≤ 2.5 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0-1.

Exclusion Criteria:

- Patients receiving treatment with an investigational agent, concurrently or within 28
days prior to dosing in this study.

- Patients with known HL or ALCL involvement of either the leptomeningeal or central
nervous system.

- Patients who received prior anti-CD30 therapy AND with anti-XmAb2513 antibodies in
serum detected by the Xencor screening assay.

- Patients requiring treatment with oral or intravenous corticosteroids or other oral
or intravenous immunosuppressive agents.

- Patients that have been designated Class III or IV by the New York Heart Association
criteria.

- Patients with a history of myocardial infarction or stroke within the last 6 months.

- Patients with known hypersensitivity to any excipient contained in the drug
formulation.

- Patients with active infection are not eligible. This includes patients requiring
anti-infective treatment during the 4 week period prior to enrollment. Patients on
prophylactic anti-infective agents will be eligible provided they have no signs of
active infection.

- Patients who are known to be HIV, Hepatitis B, or Hepatitis C positive.

- Patients with a history of prior malignancy other than HL or ALCL that have not been
in remission for greater than 5 years, with the exception of basal or squamous skin
carcinoma, cervical carcinoma in situ on biopsy, or localized prostate cancer
(Gleason score < 5).

- Patients who are pregnant or breastfeeding.

- Patients with major surgery or radiation therapy within four weeks prior to
enrollment.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Identification of the maximum tolerated dose and identification of the recommended dose of XmAb®2513 for evaluation in future studies.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Anas Younes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

XmAb2513-01

NCT ID:

NCT00606645

Start Date:

December 2007

Completion Date:

January 2010

Related Keywords:

  • Hodgkin Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Anaplastic

Name

Location

MD Anderson Cancer CenterHouston, Texas  77030-4096
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Rush University Medical CenterChicago, Illinois  60612-3824
Ohio State UniversityColumbus, Ohio  43210