High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma
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| ClinicalTrials.gov Identifier: NCT01434472 |
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Recruitment Status :
Terminated
(Terminated due to insufficient funding)
First Posted : September 15, 2011
Results First Posted : May 25, 2021
Last Update Posted : July 20, 2021
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Sponsor:
Fred Hutchinson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ajay Gopal, Fred Hutchinson Cancer Center
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Post-Transplant Lymphoproliferative Disorder Recurrent Adult Diffuse Large Cell Lymphoma Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Burkitt Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Burkitt Lymphoma Refractory Diffuse Large B-Cell Lymphoma | Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Cyclosporine Drug: Fludarabine Phosphate Radiation: Indium In-111 Ibritumomab Tiuxetan Drug: Mycophenolate Mofetil Other: Pharmacological Study Biological: Rituximab Radiation: Total-Body Irradiation Radiation: Yttrium Y-90 Ibritumomab Tiuxetan Drug: Fludarabine | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 20 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Trial of High-Dose 90Y-Ibritumomab Tiuxetan (Anti-CD20) Followed by Fludarabine and Low-Dose Total Body Irradiation and HLA-Matched Allogeneic Hematopoietic Transplantation for Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma |
| Actual Study Start Date : | November 16, 2011 |
| Actual Primary Completion Date : | May 6, 2020 |
| Actual Study Completion Date : | May 6, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
Drug Information available for:
Ibritumomab tiuxetan
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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).
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Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)
Other Names:
Drug: Cyclosporine Given PO
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Radiation: Indium In-111 Ibritumomab Tiuxetan Given IV
Other Names:
Drug: Mycophenolate Mofetil Given PO
Other Names:
Other: Pharmacological Study Correlative studies Biological: Rituximab Given IV prior to yttrium Y 90 ibritumomab tiuxetan
Other Names:
Radiation: Total-Body Irradiation Undergo TBI
Other Names:
Radiation: Yttrium Y-90 Ibritumomab Tiuxetan Given IV
Other Names:
Drug: Fludarabine Given IV
Other Names:
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Primary Outcome Measures :
- Progression-free Survival [ Time Frame: 1 year ]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.
Secondary Outcome Measures :
- Absolute Neutrophil Count (ANC) Engraftment [ Time Frame: Up to day 100 ]The median time in days to achieve ANC recovery defined as ANC>500uL.
- Overall Survival [ Time Frame: Up to 2 years post transplant ]
- Response Rates [ Time Frame: Day 100 ]Response is defined as having achieved a Partial Response or better.
- Treatment-related Mortality [ Time Frame: Day 100 ]Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.
- Platelet Engraftment [ Time Frame: Up to day 100 ]The median time in days to achieve platelet recovery as defined as platelet >20,000uL.
- Hematopoietic Toxicity [ Time Frame: Up to day 100 ]Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients must have a histologically confirmed diagnosis of aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], etc.) expressing the CD20 antigen and have failed at least one prior standard systemic therapy
- Patients must have relapsed after high-dose therapy and autologous transplantation or be ineligible for high-dose therapy and autologous transplantation; patients that have failed autologous transplantation are those with persistent disease > 30 days after transplant; those ineligible for autologous transplant include those with chemoresistant disease (i.e., patients who have not achieved a partial response or better with their most recent chemotherapy regimen), are expected to have a poor outcome from autologous transplant (e.g., DLBCL relapsing within one year of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone [R-CHOP]-like chemotherapy, double hit lymphoma, v-myc myelocytomatosis viral oncogene homolog (avian) positive [MYC+] lymphoma, persistent positron emission tomography [PET] positivity after chemotherapy), are unable to collect sufficient or tumor-free autologous stem cells per Seattle Cancer Care Alliance (SCCA) standard practice, are unable to tolerate the high-dose autologous conditioning regimens, or who refuse a high-dose autologous transplant regimen
- Creatinine (Cr) < 2.0
- Bilirubin < 1.5 mg/dL with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)
- Patients must have an expected survival without treatment of > 60 days and must be free of major infection including human immunodeficiency virus (HIV)
- Patients must have an HLA-identical related or HLA-matched unrelated donor
Exclusion Criteria:
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Receipt of systemic anti-lymphoma therapy withinthe following intervals prior to the therapeutic 90Y-ibritumomab tiuxetan dose:
- < 30 days for intravenously-administered cytotoxic chemotherapy and/or monoclonal antibodies
- < 5 half-lives for all other anti-cancer agents (e.g., targeted therapies, corticosteroids, immunomodulatory agents, etc.)
- 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)
Information from the National Library of Medicine
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): NCT01434472
Locations
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
Sponsors and Collaborators
Fred Hutchinson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Ajay Gopal | Fred Hutch/University of Washington Cancer Consortium |
Study Documents (Full-Text)
Documents provided by Ajay Gopal, Fred Hutchinson Cancer Center:
Documents provided by Ajay Gopal, Fred Hutchinson Cancer Center:
Study Protocol and Statistical Analysis Plan [PDF] May 7, 2020
| Responsible Party: | Ajay Gopal, Professor, Fred Hutchinson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01434472 |
| Other Study ID Numbers: |
2398.00 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 ) P30CA015704 ( U.S. NIH Grant/Contract ) RG9213033 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
| First Posted: | September 15, 2011 Key Record Dates |
| Results First Posted: | May 25, 2021 |
| Last Update Posted: | July 20, 2021 |
| Last Verified: | July 2021 |
Additional relevant MeSH terms:
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Burkitt Lymphoma Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoproliferative Disorders Recurrence Neoplasms by Histologic Type Neoplasms Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Attributes Pathologic Processes Epstein-Barr Virus Infections |
Herpesviridae Infections DNA Virus Infections Virus Diseases Infections Tumor Virus Infections Vidarabine Cyclosporine Mycophenolic Acid Rituximab Antineoplastic Agents, Immunological Fludarabine Fludarabine phosphate Antibodies Immunoglobulins Antibodies, Monoclonal |