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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-01189 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2398.00 | 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 | |
| RG9213033 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium |
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Terminated due to insufficient funding
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial studies the side effects and how well high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-cluster of differentiation [CD]20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) work in treating patients with aggressive B-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Radiolabeled monoclonal antibodies, such as Y-90-ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them with less effect on normal cells. Giving chemotherapy, such as fludarabine phosphate, and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. However, high-dose radiolabeled antibodies also destroy healthy blood cells in the patient's body. When healthy stem cells from a donor are infused into the patient (stem cell transplant), they may help the patient's body replace these blood cells. Giving high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, TBI, and donor PBSCT may be an effective treatment for patients with B-cell lymphoma.
PRIMARY OBJECTIVES:
I. To assess the safety and efficacy of 1.5 mCi/kg (max 120 mCi) 90Y-Ibritumomab tiuxetan (yttrium Y 90 ibritumomab tiuxetan) (anti-CD20) combined with fludarabine (fludarabine phosphate) (30 mg/m^2 x 3) and 2 gray (Gy) total body irradiation followed by human leukocyte antigens (HLA) matched allogeneic hematopoietic transplantation for patients with relapsed or refractory aggressive B-cell lymphoma.
OUTLINE:
Beginning 24-48 hours prior to therapy infusion, patients receive rituximab intravenously (IV) over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donor).
After completion of study treatment and assessments through ~day 100 following transplant, patients are followed up at 1, 3, 6, and 12 months and then annually up to 2 years thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) | Experimental | Beginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO BID on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO TID on days 0-40 with taper to day 96 (unrelated donor). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival | Based on a one-sample chi-square test with one-sided significance level of five percent. This study will be deemed successful if the 1 year progression-free survival of this highest-risk group of patients is 54% or greater. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Neutrophil Count (ANC) Engraftment | The median time in days to achieve ANC recovery defined as ANC>500uL. | Up to day 100 |
| Overall Survival | Up to 2 years post transplant |
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Inclusion Criteria:
Exclusion Criteria:
Receipt of systemic anti-lymphoma therapy withinthe following intervals prior to the therapeutic 90Y-ibritumomab tiuxetan dose:
Inability to understand or give an informed consent
Active central nervous system lymphoma
Pregnancy
Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) performance score >= 2
High-dose chemotherapy or external beam radiation therapy to lung, liver, or kidneys > 20 Gy within the previous 100 days prior to therapeutic 90Y-ibritumomab tiuxetan dose
Medical condition that would contraindicate allogeneic transplantation as per standard practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc)
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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 (Radiolabeled Antibody, TBI, Allogeneic PBSCT) | Beginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO BID on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO TID on days 0-40 with taper to day 96 (unrelated donor). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: 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_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 7, 2020 |
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| Cyclosporine | Drug | Given PO |
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| Fludarabine Phosphate | Drug | Given IV |
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| Indium In-111 Ibritumomab Tiuxetan | Radiation | Given IV |
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| Mycophenolate Mofetil | Drug | Given PO |
|
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| Pharmacological Study | Other | Correlative studies |
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| Rituximab | Biological | Given IV prior to yttrium Y 90 ibritumomab tiuxetan |
|
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| Total-Body Irradiation | Radiation | Undergo TBI |
|
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| Yttrium Y-90 Ibritumomab Tiuxetan | Radiation | Given IV |
|
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| Fludarabine | Drug | Given IV |
|
|
| Response Rates | Response is defined as having achieved a Partial Response or better. | Day 100 |
| Treatment-related Mortality | Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy. | Day 100 |
| Platelet Engraftment | The median time in days to achieve platelet recovery as defined as platelet >20,000uL. | Up to day 100 |
| Hematopoietic Toxicity | Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding. | Up to day 100 |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) | Beginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO BID on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO TID on days 0-40 with taper to day 96 (unrelated donor). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | 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 | Progression-free Survival | Based on a one-sample chi-square test with one-sided significance level of five percent. This study will be deemed successful if the 1 year progression-free survival of this highest-risk group of patients is 54% or greater. | Posted | Count of Participants | Participants | 1 year |
|
|
| |||||||||||||||||||||||||||
| Secondary | Absolute Neutrophil Count (ANC) Engraftment | The median time in days to achieve ANC recovery defined as ANC>500uL. | Posted | Median | Full Range | Days | Up to day 100 |
|
| |||||||||||||||||||||||||||
| Secondary | Overall Survival | Posted | Count of Participants | Participants | Up to 2 years post transplant |
|
| |||||||||||||||||||||||||||||
| Secondary | Response Rates | Response is defined as having achieved a Partial Response or better. | Posted | Count of Participants | Participants | Day 100 |
|
| ||||||||||||||||||||||||||||
| Secondary | Treatment-related Mortality | Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy. | Posted | Count of Participants | Participants | Day 100 |
|
| ||||||||||||||||||||||||||||
| Secondary | Platelet Engraftment | The median time in days to achieve platelet recovery as defined as platelet >20,000uL. | Posted | Median | Full Range | Days | Up to day 100 |
|
| |||||||||||||||||||||||||||
| Secondary | Hematopoietic Toxicity | Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding. | Posted | Number | Incidences | Up to day 100 |
|
|
AEs will be collected from the time of first exposure to a study intervention (i.e., the start of the rituximab infusion associated with the therapy dose) through day +100 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician.
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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 (Radiolabeled Antibody, TBI, Allogeneic PBSCT) | Beginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO BID on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO TID on days 0-40 with taper to day 96 (unrelated donor). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV | 6 | 20 | 11 | 20 | 11 | 20 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thromboembolic event - cerebal infarct | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Wound Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute Renal Injury | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Adenovirus pneumonia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| ARDS | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Ascites | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| E. coli bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Enterocolitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Extrapyramidal disorder | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Blood infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Neutropenic fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ajay Gopal | Fred Hutchinson Cancer Research Center | 206-606-2037 | agopal@uw.edu |
| Apr 28, 2021 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D016393 | Lymphoma, B-Cell |
| D002051 | Burkitt Lymphoma |
| 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 |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D003524 | Cyclosporins |
| C042382 | fludarabine phosphate |
| D007204 | Indium |
| D009173 | Mycophenolic Acid |
| D000069283 | Rituximab |
| C000626854 | CT-P10 |
| D014916 | Whole-Body Irradiation |
| C422802 | ibritumomab tiuxetan |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D008670 | Metals |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D008919 | Investigative Techniques |
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| Unknown or Not Reported |
|
| 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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