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A Phase I Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Phase I Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by Autologous Stem Cell Transplantation for Relapsed or Refractory Lymphoid Malignancies


PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose (MTD) of 90Y-BC8-DOTA (anti-cluster of
differentiation [CD]45) (yttrium-90 anti-CD45 monoclonal antibody BC8) that can be delivered
prior to autologous stem cell transplantation for patients with relapsed/refractory B-cell
non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), and Hodgkin lymphoma (HL).

SECONDARY OBJECTIVES:

I. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in
the majority of patients.

II. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden
on CD20 and CD45 targeting.

III. To describe response rates and remission durations in relapsed B-NHL, T-NHL, and HL
following administration of myeloablative doses of 90Y-BC8-DOTA prior to autologous stem
cell transplant (ASCT).

IV. To assess the correlation of lymphoma biomarkers with outcomes.

OUTLINE: This is a dose-escalation study of yttrium-90 anti-CD45 monoclonal antibody BC8.

Patients receive indium-111 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -28
and (if necessary) day -21 to evaluate the antibody's biodistribution. Patients then receive
yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients then undergo autologous
peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 3, 6, and 12 months and
then annually thereafter.


Inclusion Criteria:



- Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45
antigen expression must be documented on tumor specimens in all cases except HL, in
whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is
required; patients must have received at least one prior standard systemic therapy
with documented recurrent or refractory disease; patients with mantle cell lymphoma
(MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in
complete remission (CR)/first partial remission (PR1)

- Creatinine < 2.0

- Bilirubin < 1.5 mg/dL

- All patients eligible for therapeutic study must have a minimum of >/= 2 x10^6
CD34/kg autologous hematopoietic stem cells harvested and cryopreserved

- Patients must have an expected survival of > 60 days and must be free of major
infection

- Patients are preferred to have either a tumor mass amenable to core needle biopsy
during the dosimetry phase, or a measurable tumor mass with at least one site of
involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging
for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT
tumor dosimetry

Exclusion Criteria:

- Circulating human anti-mouse antibody (HAMA), to be determined before each infusion

- Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled
therapy dose with the exception of rituximab

- Inability to understand or give an informed consent

- Lymphoma involving the central nervous system

- Other serious medical conditions considered to represent contraindications to ASCT
(e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung
for carbon monoxide [DLCO] < 50% predicted, acquired immune deficiency syndrome
[AIDS], etc.)

- Known human immunodeficiency virus (HIV) seropositivity

- Pregnancy or breast feeding

- Prior allogeneic bone marrow or stem cell transplant

- Prior autologous bone marrow or stem cell transplant within 1 year of enrollment

- Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of
enrollment

- Southwest Oncology Group (SWOG) performance status >/= 2.0

- Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved
a positron emission tomography (PET)-negative CR following first salvage chemotherapy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

MTD of yttrium-90 anti-CD45 monoclonal antibody BC8 before stem cell transplant defined as dose-limiting toxicity rate of 25% graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Outcome Time Frame:

Up to 30 days after receiving study drug

Safety Issue:

Yes

Principal Investigator

Ajay Gopal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2361.00

NCT ID:

NCT01678443

Start Date:

December 2012

Completion Date:

Related Keywords:

  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Hairy Cell Leukemia
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Hairy Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell
  • Leukemia, Large Granular Lymphocytic

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109