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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Post-transplant Lymphoproliferative Disorder, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma

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Trial Information

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


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 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:

Patients receive a dosimetry test dose of indium In 111 ibritumomab tiuxetan intravenously
(IV) within four weeks prior to transplant and then receive a therapy-dose of high-dose
yttrium Y 90 ibritumomab tiuxetan IV on day -14 prior to transplant. Both ibritumomab
tiuxetan infusions may be preceded by rituximab IV, depending on results of blood tests to
determine rituximab concentration. Patients 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 thereafter.


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 R-CHOP,
double hit lymphoma, MYC+ lymphoma, persistent 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 < 1.5mg/dL with the exception of patients thought to have Gilbert's
syndrome, who may have a total bilirubin above 1.5mg/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

- Patients must be >= 18 years old

Exclusion Criteria:

- Systemic anti-lymphoma therapy given within 30 days prior to therapeutic
90Y-ibritumomab tiuxetan dose

- Inability to understand or give an informed consent

- 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)

- Altered biodistribution (determined following trace-labeled 111In-ibritumomab
tiuxetan dose)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Outcome 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 PFS of this highest-risk group of patients is 54% or greater.

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Ajay Gopal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2398.00

NCT ID:

NCT01434472

Start Date:

November 2011

Completion Date:

Related Keywords:

  • Post-transplant Lymphoproliferative Disorder
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Burkitt Lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, Extranodal NK-T-Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109