Trial Outcomes & Findings for High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma (NCT NCT01434472)

Last Updated: 2021-07-20

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

1 year

Results posted on

2021-07-20

Participant Flow

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	20
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	52.5 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Progression-free Survival	11 Participants

SECONDARY outcome

Timeframe: Up to day 100

The median time in days to achieve ANC recovery defined as ANC\>500uL.

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Absolute Neutrophil Count (ANC) Engraftment	16 Days Interval 7.0 to 24.0

SECONDARY outcome

Timeframe: Up to 2 years post transplant

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Overall Survival	14 Participants

SECONDARY outcome

Timeframe: Day 100

Response is defined as having achieved a Partial Response or better.

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Response Rates	16 Participants

SECONDARY outcome

Timeframe: Day 100

Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Treatment-related Mortality	1 Participants

SECONDARY outcome

Timeframe: Up to day 100

The median time in days to achieve platelet recovery as defined as platelet \>20,000uL.

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Platelet Engraftment	9 Days Interval 0.0 to 21.0

SECONDARY outcome

Timeframe: Up to day 100

Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.

Outcome measures

Outcome measures
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 Participants 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
Hematopoietic Toxicity	5 Incidences

Adverse Events

Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)

Serious events: 11 serious events

Other events: 11 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 participants at risk 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
Vascular disorders Thromboembolic event - cerebal infarct	5.0% 1/20 • Number of events 1 • 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.
Infections and infestations Wound Infection	5.0% 1/20 • Number of events 1 • 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.
Gastrointestinal disorders Abdominal Pain	10.0% 2/20 • Number of events 2 • 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.
Investigations Acute Renal Injury	10.0% 2/20 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders Adenovirus pneumonia	5.0% 1/20 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders ARDS	5.0% 1/20 • Number of events 2 • 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.
Respiratory, thoracic and mediastinal disorders Ascites	5.0% 1/20 • Number of events 1 • 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.
Gastrointestinal disorders Diarrhea	10.0% 2/20 • Number of events 3 • 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.
Nervous system disorders Dizziness	5.0% 1/20 • Number of events 1 • 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.
Infections and infestations E. coli bacteremia	5.0% 1/20 • Number of events 1 • 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.
Gastrointestinal disorders Enterocolitis	5.0% 1/20 • Number of events 1 • 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.
Nervous system disorders Extrapyramidal disorder	5.0% 1/20 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Hypoxia	5.0% 1/20 • Number of events 1 • 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.
Infections and infestations Blood infection	10.0% 2/20 • Number of events 2 • 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.
Infections and infestations Neutropenic fever	15.0% 3/20 • Number of events 5 • 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.

Other adverse events

Other adverse events
Measure	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT) n=20 participants at risk 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
Gastrointestinal disorders Anorexia	10.0% 2/20 • Number of events 2 • 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.
General disorders Fatigue	15.0% 3/20 • Number of events 3 • 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.
Metabolism and nutrition disorders Hypophosphatemia	20.0% 4/20 • Number of events 4 • 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.
Skin and subcutaneous tissue disorders Rash	25.0% 5/20 • Number of events 5 • 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.

Additional Information

Dr. Ajay Gopal

Fred Hutchinson Cancer Research Center

Phone: 206-606-2037

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place