High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

Recurrent Adult Diffuse Large Cell Lymphoma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT01434472
• Other study ID #: 2398.00
• Secondary ID: NCI-2011-0118923
• Status: Terminated
• Phase: Phase 2
• Start date: November 16, 2011
• Est. completion date: May 6, 2020

Study information

• Verified date: July 2021
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: May 6, 2020
• Est. primary completion date: May 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin
• Lymphoproliferative Disorders
• 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

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)

Drug:
• Cyclosporine
Given PO
• Fludarabine Phosphate
Given IV

Radiation:
• Indium In-111 Ibritumomab Tiuxetan
Given IV

Drug:
• Mycophenolate Mofetil
Given PO

Other:
• Pharmacological Study
Correlative studies

Biological:
• Rituximab
Given IV prior to yttrium Y 90 ibritumomab tiuxetan

Radiation:
• Total-Body Irradiation
Undergo TBI
• Yttrium Y-90 Ibritumomab Tiuxetan
Given IV

Drug:
• Fludarabine
Given IV

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	1 year
Secondary	Absolute Neutrophil Count (ANC) Engraftment	The median time in days to achieve ANC recovery defined as ANC>500uL.	Up to day 100
Secondary	Overall Survival		Up to 2 years post transplant
Secondary	Response Rates	Response is defined as having achieved a Partial Response or better.	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.	Day 100
Secondary	Platelet Engraftment	The median time in days to achieve platelet recovery as defined as platelet >20,000uL.	Up to day 100
Secondary	Hematopoietic Toxicity	Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.	Up to day 100