Description:
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.
Title
- Brief Title: High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma
- 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
Clinical Trial IDs
- ORG STUDY ID:
2398.00
- SECONDARY ID:
NCI-2011-01189
- SECONDARY ID:
2398.00
- SECONDARY ID:
P01CA044991
- SECONDARY ID:
P30CA015704
- SECONDARY ID:
RG9213033
- NCT ID:
NCT01434472
Conditions
- 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
Interventions
Drug | Synonyms | Arms |
---|
Cyclosporine | 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya | Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) |
Fludarabine Phosphate | 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586 | Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) |
Mycophenolate Mofetil | Cellcept, MMF | Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) |
Rituximab | ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83 | Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) |
Fludarabine | 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine, Fluradosa | Treatment (radiolabeled antibody, TBI, allogeneic PBSCT) |
Purpose
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.
Detailed Description
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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). | - Cyclosporine
- Fludarabine Phosphate
- Mycophenolate Mofetil
- Rituximab
- Fludarabine
|
Eligibility 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:
- 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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free Survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | 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
Measure: | Absolute Neutrophil Count (ANC) Engraftment |
Time Frame: | Up to day 100 |
Safety Issue: | |
Description: | The median time in days to achieve ANC recovery defined as ANC>500uL. |
Measure: | Overall Survival |
Time Frame: | Up to 2 years post transplant |
Safety Issue: | |
Description: | |
Measure: | Response Rates |
Time Frame: | Day 100 |
Safety Issue: | |
Description: | Response is defined as having achieved a Partial Response or better. |
Measure: | Treatment-related Mortality |
Time Frame: | Day 100 |
Safety Issue: | |
Description: | Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy. |
Measure: | Platelet Engraftment |
Time Frame: | Up to day 100 |
Safety Issue: | |
Description: | The median time in days to achieve platelet recovery as defined as platelet >20,000uL. |
Measure: | Hematopoietic Toxicity |
Time Frame: | Up to day 100 |
Safety Issue: | |
Description: | Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Fred Hutchinson Cancer Research Center |
Last Updated
July 20, 2021