Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies
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
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
Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
Procedure: peripheral blood stem cell transplantation
Procedure: autologous hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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|
- 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% [ Time Frame: Within 30 days post-transplant ] [ Designated as safety issue: Yes ]DLT is defined as a therapy-related grade III or IV Bearman (transplant) toxicity.
- Progression-free survival following ASCT [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]A favorable biodistribution in a given patient will be defined by the target tissue receiving higher radiation dose per unit-administered activity (cGy/mCi) relative to all critical normal organs (lung, liver, kidney, etc.).
- 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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2013|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)
Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours 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 PBSC transplant on day 0.
Radiation: yttrium Y 90 anti-CD45 monoclonal antibody BC8
Other Names:Drug: carmustine
Other Names:Drug: etoposide
Other Names:Drug: cytarabine
Other Names:Drug: melphalan
Other Names:Procedure: peripheral blood stem cell transplantation
Undergo autologous PBSC transplant
Other Names:Procedure: autologous hematopoietic stem cell transplantation
Undergo autologous PBSC transplantOther: laboratory biomarker analysis
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01921387
|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 firstname.lastname@example.org|
|Principal Investigator: Ajay K. Gopal|
|Principal Investigator:||Ajay Gopal||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|