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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Terminated; Phase 1

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

Treatments: Biological: indium In 111 anti-CD45 monoclonal antibody BC8; Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8; Procedure: peripheral blood stem cell transplantation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01678443

NCI-2012-01505 (Registry Identifier)

P01CA044991 (U.S. NIH Grant/Contract)

2361.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

2 participants in 1 patient group

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

Experimental group

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.

Treatment:

Procedure: peripheral blood stem cell transplantation

Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8

Biological: indium In 111 anti-CD45 monoclonal antibody BC8