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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2013-01378 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2728.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| P01CA044991 | U.S. NIH Grant/Contract | View source | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (90Y-BC8-DOTA, chemotherapy, PBSC) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous Hematopoietic Stem Cell Transplantation | Procedure | Undergo autologous PBSC transplant |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA | 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. | Within 30 days post-transplant |
| Progression-free Survival Following Autologous Stem Cell Transplant (ASCT) | Estimate the 1 year progression-free survival (PFS) rate after ASCT | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Will be evaluated among all patients and among those treated at the estimated MTD. | Up to 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ajay Gopal | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 4, 2017 | Jul 17, 2018 |
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| Carmustine | Drug | Given IV |
|
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| Cytarabine | Drug | Given IV |
|
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| Etoposide | Drug | Given IV |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
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| Melphalan | Drug | Given IV |
|
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| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo autologous PBSC transplant |
|
|
| Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 | Radiation | Given IV |
|
|
| The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients |
| Up to 5 years |
| COMPLETED |
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| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA | 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. | Posted | Number | Gy - MTD | Within 30 days post-transplant |
|
|
| |||||||||||||||||||||||||||
| Primary | Progression-free Survival Following Autologous Stem Cell Transplant (ASCT) | Estimate the 1 year progression-free survival (PFS) rate after ASCT | Posted | Count of Participants | Participants | 1 year |
|
| ||||||||||||||||||||||||||||
| Secondary | 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 | Will be evaluated among all patients and among those treated at the estimated MTD. | Posted | Number | mCi | Up to 5 years |
|
| ||||||||||||||||||||||||||||
| Secondary | The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients | Posted | Number | mg/kg | Up to 5 years |
|
|
AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV | 5 | 20 | 20 | 20 | 0 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Anaphylaxis | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Chest pain | Cardiac disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Fever | General disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment | Grade 2 and Grade 4 |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 and Grade 4 |
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| Engraftment syndrome | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Blood infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Peripheral neuropathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Serum sickness | Immune system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
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| Sinusitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Syncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | Grade 3 |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ajay Kumar Gopal, MD, Director of Clinical Research | Seattle Cancer Care Alliance | (206) 606-2037 | agopal@uw.edu.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 4, 2017 | Jul 17, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D006689 | Hodgkin Disease |
| D020522 | Lymphoma, Mantle-Cell |
| D016399 | Lymphoma, T-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D002330 | Carmustine |
| C574855 | carmustine, poliferprosan 20 drug combination |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| D008558 | Melphalan |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
|
| More than one race |
|
| Unknown or Not Reported |
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