Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies - Full Text View

Purpose

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.

Condition	Intervention	Phase
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	Biological: indium In 111 anti-CD45 monoclonal antibody BC8 Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8 Procedure: peripheral blood stem cell transplantation	Phase 1


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

Resource links provided by NLM:

Genetics Home Reference related topics: Sézary syndrome Waldenström macroglobulinemia mycosis fungoides

MedlinePlus related topics: Cancer Leukemia

Drug Information available for: Yttrium Indium

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Hodgkin Lymphoma Waldenstrom Macroglobulinemia Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Follicular Lymphoma Lymphoma, Large-cell B-cell Lymphoma Burkitt Lymphoma Anaplastic Large Cell Lymphoma Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Mycosis Fungoides Hairy Cell Leukemia Cutaneous T-cell Lymphoma Lymphoblastic Lymphoma Peripheral T-cell Lymphoma Large Granular Lymphocyte Leukemia Aggressive NK Cell Leukemia Leukemia, T-cell, Chronic Sezary Syndrome Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Adult T-cell Leukemia/lymphoma Lymphomatoid Granulomatosis Acute Lymphoblastic Leukemia

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

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 v4.0 [ Time Frame: Up to 30 days after receiving study drug ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall response rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
Progression-free survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
Tumor to normal organ ratios [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.


Enrollment:	2
Study Start Date:	December 2012
Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8) 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.	Biological: indium In 111 anti-CD45 monoclonal antibody BC8 Given IV Other Names: In 111 MOAB BC8 In 111 monoclonal antibody BC8 In111 MOAB BC8 indium In 111 MOAB BC8 Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8 Given IV Other Names: 90Y anti-CD45 MAb BC8 90Y anti-CD45 MoAb BC8 Procedure: peripheral blood stem cell transplantation Undergo autologous peripheral blood stem cell transplant Other Names: PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell

Arms

Assigned Interventions

Experimental: Treatment (yttrium-90 anti-CD45 monoclonal antibody BC8)

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.

Biological: indium In 111 anti-CD45 monoclonal antibody BC8

Given IV

Other Names:

In 111 MOAB BC8
In 111 monoclonal antibody BC8
In111 MOAB BC8
indium In 111 MOAB BC8

Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8

Given IV

Other Names:

90Y anti-CD45 MAb BC8
90Y anti-CD45 MoAb BC8

Procedure: peripheral blood stem cell transplantation

Undergo autologous peripheral blood stem cell transplant

Other Names:

PBPC transplantation
PBSC transplantation
peripheral blood progenitor cell transplantation
transplantation, peripheral blood stem cell

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01678443

Locations


United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Ajay Gopal	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information


Responsible Party:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT01678443 History of Changes
Other Study ID Numbers:	2361.00 NCI-2012-01505 2361.00 P01CA044991 P30CA015704
Study First Received:	August 31, 2012
Last Updated:	December 7, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Lymphoma Leukemia Lymphoma, Non-Hodgkin Lymphoma, Follicular Hodgkin Disease Lymphoma, B-Cell Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Large B-Cell, Diffuse Leukemia, Lymphocytic, Chronic, B-Cell Precursor Cell Lymphoblastic Leukemia-Lymphoma Burkitt Lymphoma Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Lymphoma, T-Cell	Mycoses Mycosis Fungoides Sezary Syndrome Lymphoma, T-Cell, Cutaneous Leukemia, T-Cell Waldenstrom Macroglobulinemia Lymphoma, Large-Cell, Anaplastic Leukemia-Lymphoma, Adult T-Cell Leukemia, Hairy Cell Lymphoma, Extranodal NK-T-Cell Lymphoma, T-Cell, Peripheral Lymphomatoid Granulomatosis Immunoblastic Lymphadenopathy Intraocular Lymphoma Leukemia, Large Granular Lymphocytic

ClinicalTrials.gov processed this record on September 28, 2016