Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies
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|ClinicalTrials.gov Identifier: NCT01921387|
Recruitment Status : Active, not recruiting
First Posted : August 13, 2013
Results First Posted : September 3, 2018
Last Update Posted : September 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Hodgkin Lymphoma Recurrent Mantle Cell Lymphoma Recurrent T-Cell Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Hodgkin Lymphoma Refractory Mantle Cell Lymphoma Refractory T-Cell Non-Hodgkin Lymphoma||Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Drug: Cytarabine Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Melphalan Procedure: Peripheral Blood Stem Cell Transplantation Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 9, 2013|
|Actual Primary Completion Date :||July 26, 2017|
|Estimated Study Completion Date :||July 26, 2021|
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.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC transplant
Other Name: autologous stem cell transplantation
Other: Laboratory Biomarker Analysis
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSC transplant
Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Other Name: 90Y Anti-CD45 MoAb BC8
- Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA [ Time Frame: Within 30 days post-transplant ]Single patients will be treated at escalating doses in 2-Gy increments (Table 4) until a DLT is observed. Once a DLT is observed, the second stage will begin at the next lower dose level and patients will be treated in cohorts of 4.
- Progression-free Survival Following Autologous Stem Cell Transplant (ASCT) [ Time Frame: 1 year ]Estimate the 1 year progression-free survival (PFS) rate after ASCT
- 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 ]Will be evaluated among all patients and among those treated at the estimated MTD.
- The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients [ Time Frame: Up to 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01921387
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Ajay Gopal||Fred Hutch/University of Washington Cancer Consortium|