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Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; 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 Acute Lymphoblastic Leukemia; 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 Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Intervention: yttrium Y 90 anti-CD45 monoclonal antibody BC8 (Radiation); carmustine (Drug); etoposide (Drug); cytarabine (Drug); melphalan (Drug); peripheral blood stem cell transplantation (Procedure); autologous hematopoietic stem cell transplantation (Procedure); laboratory biomarker analysis (Other)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Ajay Gopal, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Summary

This phase I/II trial studies the side effects and the best dose of radiolabeled monoclonal antibody when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with high-risk lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy before a stem transplant stops the growth of cancer cells by stopping them from dividing or killing them. Stem cells collected from the patient's blood are then returned to the patient to replace the blood-forming cells that were destroyed by the radiolabeled monoclonal antibody and chemotherapy.

Clinical Details

Official title: A Phase I/II Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Lymphoid Malignancies

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

MTD of yttrium Y 90 anti-CD45 monoclonal antibody BC8, defined as the dose that is associated with a true dose-limiting toxicity (DLT) rate of 25%

Progression-free survival following ASCT

Secondary outcome:

The lowest antibody (yttrium Y 90 anti-CD45 monoclonal antibody BC8) dose (mg/kg) that is consistent with a favorable biodistribution rate >= 80% in lymphoma patients

Estimated dose to tumor sites based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 anti-CD45 monoclonal antibody BC8

Detailed description: PRIMARY OBJECTIVES: I. To estimate the maximum-tolerated dose (MTD) of 90Y-BC8-DOTA (yttrium Y 90 anti-CD45 monoclonal antibody BC8) (anti-cluster of differentiation [CD] 45) that can be delivered prior to myeloablative carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplant (ASCT) for patients with high-risk B-non-Hodgkin lymphoma (NHL), T-NHL, and Hodgkin lymphoma (HL). II. To evaluate the efficacy of 90Y-BC8-DOTA when administered at the estimated MTD prior to BEAM chemotherapy and ASCT for patients with high-risk B-NHL, T-NHL, and HL compared to historical controls treated with BEAM alone. SECONDARY OBJECTIVES: I. To describe the toxicity observed from the addition of 90Y-BC8-DOTA to BEAM. II. To optimize the protein dose (Ab) to deliver a favorable biodistribution in the majority of patients. III. To describe response rates and overall survival of patients with high-risk B-NHL, T-NHL, and HL following administration of 90Y-BC8-DOTA plus BEAM prior to ASCT. IV. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD45 targeting. V. To assess the correlation of lymphoma biomarkers with outcomes. VI. To evaluate the effects of nodal-targeted irradiation by 90Y-BC8-DOTA on immune reconstitution following ASCT. OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 followed by a phase II study. Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day

- 14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours

twice daily (BID) on days - 6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and

melphalan IV over 30 minutes on day - 2. Patients then undergo autologous peripheral blood

stem cell (PBSC) transplant on day 0. After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually thereafter.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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 x10^6 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 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 carbon monoxide [DLCO] < 50% predicted, etc.)

- Known human immunodeficiency virus (HIV) seropositivity

- Pregnancy or breast feeding

- Prior autologous or allogeneic bone marrow or stem cell transplant

- Prior radiation therapy (RT) > 20 gray (Gy) to a critical organ within 1 year of

enrollment

- Southwestern Oncology Group (SWOG) performance status >= 2. 0

Locations and Contacts

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Ajay K. Gopal, Phone: 206-288-2037
Ajay K. Gopal, Principal Investigator
Additional Information

Starting date: October 2013
Last updated: June 22, 2015

Page last updated: August 23, 2015

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