Brief Title
Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
Official Title
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
Brief Summary
This phase I trial studies the side effects and best dose of monoclonal antibody therapy
before stem cell transplant in treating patients with relapsed or refractory lymphoid
malignancies. Radiolabeled monoclonal antibodies, such as yttrium-90 anti-CD45 monoclonal
antibody BC8, can find cancer cells and carry cancer-killing substances to them without
harming normal cells. When the healthy stem cells from a donor are infused into the patient
they may help the patient's bone marrow make stem cells, red blood cells, white blood cells,
and platelets. Giving radiolabeled monoclonal antibody before a stem cell transplant may be
an effective treatment for relapsed or refractory lymphoid malignancies.
Detailed Description
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45
Secondary Outcome
Overall Response Rate
Condition
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Intervention
indium In 111 anti-CD45 monoclonal antibody BC8
Study Arms / Comparison Groups
Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8)
Description: Patients receive indium-111 anti-CD45 monoclonal antibody BC8 IV on day -28 and (if necessary) day -21. Patients receive yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -28, -14, and -13. Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
2
Start Date
September 1, 1999
Completion Date
September 27, 2018
Primary Completion Date
September 21, 2013
Eligibility Criteria
Inclusion Criteria:
- Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only
patients with classical HL must have documented histologic demonstration of CD45+
cells adjacent to the Reed Sternberg cells; 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 x 10^6 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ajay Gopal, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01678443
Organization ID
2361.00
Secondary IDs
NCI-2012-01505
Responsible Party
Principal Investigator
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
March 2021