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: head and neck squamous cell carcinoma mycosis fungoides Sézary syndrome

MedlinePlus related topics: Cancer Fungal Infections Leukemia Lymphoma

Drug Information available for: Yttrium Indium

Genetic and Rare Diseases Information Center resources: Anaplastic Large Cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Cutaneous T-cell Lymphoma Follicular Lymphoma Hairy Cell Leukemia Hodgkin Lymphoma Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Mycosis Fungoides Peripheral T-cell Lymphoma Plasmablastic Lymphoma Sezary Syndrome Small Non-cleaved Cell Lymphoma Squamous Cell Carcinoma of the Head and Neck Waldenstrom Macroglobulinemia

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.


Estimated Enrollment:	52
Study Start Date:	December 2012
Estimated Primary Completion Date:	June 2018 (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
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	Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal 206-288-2037
Principal Investigator: Ajay K. Gopal

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

No publications provided


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:	February 20, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Burkitt Lymphoma Hodgkin Disease Immunoblastic Lymphadenopathy Intraocular Lymphoma Leukemia Leukemia, Hairy Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Follicular	Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphomatoid Granulomatosis Mycosis Fungoides Sezary Syndrome Waldenstrom Macroglobulinemia Blood Protein Disorders Cardiovascular Diseases DNA Virus Infections

ClinicalTrials.gov processed this record on February 25, 2015