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

Recurrent Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01678443
• Other study ID #: 2361.00
• Secondary ID: NCI-2012-0150523
• Status: Terminated
• Phase: Phase 1
• Start date: September 1, 1999
• Est. completion date: September 27, 2018

Study information

• Verified date: March 2021
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: September 27, 2018
• Est. primary completion date: September 21, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adult Nasal Type Extranodal NK/T-cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Burkitt Lymphoma
• Cutaneous B-cell Non-Hodgkin Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Hepatosplenic T-cell Lymphoma
• Hodgkin Disease
• Intraocular Lymphoma
• Leukemia
• Leukemia, Hairy Cell
• 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
• Mycoses
• Mycosis Fungoides
• Nodal Marginal Zone B-cell Lymphoma
• Noncutaneous Extranodal Lymphoma
• Peripheral T-cell Lymphoma
• Plasmablastic Lymphoma
• Precursor Cell Lymphoblastic Leukemia-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
• Sezary Syndrome
• Small Intestine Lymphoma
• Splenic Marginal Zone Lymphoma
• T-cell Large Granular Lymphocyte Leukemia
• Testicular Lymphoma
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Biological:
• indium In 111 anti-CD45 monoclonal antibody BC8
Given IV

Radiation:
• yttrium Y 90 anti-CD45 monoclonal antibody BC8
Given IV

Procedure:
• peripheral blood stem cell transplantation
Undergo autologous peripheral blood stem cell transplant

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicities (DLT) of Yttrium-90 Anti-CD45	A DLT (dose limiting toxicity) is defined as a therapy-related grade III or IV Bearman (transplant) toxicity within 30 days of transplant.	Up to 30 days after receiving study drug
Secondary	Overall Response Rate		Up to 6 years
Secondary	Overall Survival		Up to 6 years
Secondary	Progression-free Survival		Up to 6 years
Secondary	Tumor to Normal Organ Ratios	Derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of 90Y.	Up to 6 years