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

Study Description

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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.

Condition or disease	Intervention/treatment	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

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Actual Study Start Date :	September 1, 1999
Actual Primary Completion Date :	April 11, 2011
Estimated Study Completion Date :	July 24, 2019

Arms and Interventions

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Arm

Intervention/treatment

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

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45 [ Time Frame: Up to 30 days after receiving study drug ]
   A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.

Secondary Outcome Measures :

1. Overall Response Rate [ Time Frame: Up to 6 years ]
2. Overall Survival [ Time Frame: Up to 6 years ]
3. Progression-free Survival [ Time Frame: Up to 6 years ]
4. Tumor to Normal Organ Ratios [ Time Frame: Up to 6 years ]
   Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT01678443 History of Changes
Other Study ID Numbers:	2361.00; NCI-2012-01505 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2361.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ); P01CA044991 ( U.S. NIH Grant/Contract ); P30CA015704 ( U.S. NIH Grant/Contract )
First Posted:	September 5, 2012
Results First Posted:	November 9, 2017
Last Update Posted:	November 9, 2017
Last Verified:	October 2017

Additional relevant MeSH terms:

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