Trial Outcomes & Findings for Intensive Consolidation and Stem Cell Mobilization Therapy Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (NCT NCT01555541)

Last Updated: 2022-06-29

Results Overview

CR will be calculated based on the PET/CT scan following 2 cycles of salvage therapy using the revised International Working Group (IWG) Criteria for a lymphoma response. This includes: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, Post-treatment residual mass of any size is permitted as long as it is PET-, Spleen and/or liver, if enlarged before therapy based on physical exam or CT scan, should not be palpable on physical exam and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, If bone marrow was involved by lymphoma before treatment, infiltrate must have cleared on repeat bone marrow biopsy. Biopsy sample must be adequate (with goal of \> 20 mm unilateral core). If sample is indeterminate by morphology, it should be negative by immunohistochemistry. A sample that is negative by immunohistochemistry but demonstrates small population of clonal l

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Day 42

Results posted on

2022-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 Carmustine (BCNU) 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Salvage Response Assessment STARTED	19
Salvage Response Assessment COMPLETED	19
Salvage Response Assessment NOT COMPLETED	0
OVA Treatment STARTED	19
OVA Treatment COMPLETED	19
OVA Treatment NOT COMPLETED	0
Autologous Stem Cell Transplantation STARTED	12
Autologous Stem Cell Transplantation COMPLETED	12
Autologous Stem Cell Transplantation NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Intensive Consolidation and Stem Cell Mobilization Therapy Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Age, Customized 20-29 years	1 Participants n=5 Participants
Age, Customized 30-39 years	1 Participants n=5 Participants
Age, Customized 40-49 years	4 Participants n=5 Participants
Age, Customized 50-59 years	7 Participants n=5 Participants
Age, Customized 60-69 years	6 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 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	3 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	12 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants
Cancer Stage at Diagnosis Stage I - II	5 Participants n=5 Participants
Cancer Stage at Diagnosis Stage III - IV	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 42

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization	10 Participants

PRIMARY outcome

Timeframe: Day 42

Number of patients achieving maCR to the treatment upon successful stem cell mobilization, defined as at least 2 x10\^6 cluster of differentiation 34 (CD34)+cells/Kg of actual body weight. Patients who require use of plerixafor or an autologous bone marrow harvest are considered mobilization failures and will be treated as non-responders.

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Patients Achieving Mobilization-adjusted Complete Response (maCR)	10 Participants

SECONDARY outcome

Timeframe: Up to 5 months

Determination of CR or PR must meet the revised International Working Group (IWG) Criteria for lymphoma response

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Patients Who Received OVA and Then Met Criteria to Proceed to ASCT and Achieved a CR/Partial Response (PR) Post-ASCT	11 Participants

SECONDARY outcome

Timeframe: Up to 5 months

Population: 7 Patients were evaluable for PR after salvage

Fluorodeoxyglucose-positron emission tomography (FDG-PET) conversion rate was used determined the number of participants who improved following OVA Treatment.

Outcome measures

Outcome measures
Measure	Treatment n=7 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Patients Who Advance From Partial Response (PR) to Complete (CR)	2 Participants

SECONDARY outcome

Timeframe: Up to 24 months after ASCT

Population: Participants who received autologous transplant

Neutrophil engraftment is defined as the first day of 3 consecutive days with absolute neutrophil count of \>500 cells/microlitre (uL). Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter

Outcome measures

Outcome measures
Measure	Treatment n=12 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Participants With Successful Neutrophil Engraftments	12 participants

SECONDARY outcome

Timeframe: Up to 24 months after ASCT

Population: Participants who received autologous transplant

Platelet engraftment is defined as the first of three consecutive measurements for which the platelet count was \> 20,000/uL, and must be at least 24 hours following the last platelet transfusion. Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months after ASCT

Outcome measures

Outcome measures
Measure	Treatment n=12 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Number of Participants With Successful Platelet Engraftments	12 participants

SECONDARY outcome

Timeframe: Up to 48 months

Population: Participants receiving OVA

Time to progression (TTP) is defined as the time from treatment after OVA until documented lymphoma progression or receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy) or death due to lymphoma. Patients are to be censored at the time of last followup or death due to another cause

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Median Time to Progression	13.2 months Interval 1.4 to 48.0

SECONDARY outcome

Timeframe: Up to 24 months

The percentage of participants in the study still alive at time of censoring. The time frame defined as the time from day 0 of OVA treatment until lymphoma progression, receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy), or death as a result of any cause. Patients will be censored at the time of median follow-up.

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Progression Free Survival Rate	47 percentage of participants Interval 24.0 to 67.0

SECONDARY outcome

Timeframe: Up to 24 months

The percentage of participants in the study still alive at time of censoring. The time frame is defined as the time from day 0 of OVA treatment until death as a result of any cause. Patients will be censored at the time of last followup

Outcome measures

Outcome measures
Measure	Treatment n=19 Participants OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Overall Survival Rate (OS)	59 percentage of participants Interval 33.0 to 78.0

Adverse Events

Treatment

Serious events: 4 serious events

Other events: 9 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=19 participants at risk OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Gastrointestinal disorders Anal Pain	5.3% 1/19 • Number of events 2 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.3% 1/19 • Number of events 1 • Up to 5 years
Infections and infestations Sepsis	5.3% 1/19 • Number of events 1 • Up to 5 years
Immune system disorders Allergic reaction	5.3% 1/19 • Number of events 1 • Up to 5 years

Other adverse events

Other adverse events
Measure	Treatment n=19 participants at risk OVA Treatment: Ofatumumab: 1000 mg IV days 0, 7, 14, 21 Etoposide: 10 mg/Kg IV over 24 hours daily, days 1-4 Cytarabine: 2000 mg/m2 IV twice daily, days 1-4 \--------- After Day 42 assessment: Autologous Transplantation: Stem Cell Infusion on day 0 BCNU 15 mg/Kg, day -6 Etoposide 60 mg/Kg, day -4 Cyclophosphamide: 100 mg/Kg, day -2
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • Up to 5 years
Vascular disorders Thromboembolic event	5.3% 1/19 • Number of events 1 • Up to 5 years
Metabolism and nutrition disorders Hyponatremia	5.3% 1/19 • Number of events 1 • Up to 5 years
Psychiatric disorders Insomnia	5.3% 1/19 • Number of events 1 • Up to 5 years
Investigations Platelet count decreased	47.4% 9/19 • Number of events 12 • Up to 5 years
Investigations Neutrophil count decreased	42.1% 8/19 • Number of events 11 • Up to 5 years
Investigations White blood cell decreased	21.1% 4/19 • Number of events 5 • Up to 5 years
Investigations Alanine aminotransferase increased	5.3% 1/19 • Number of events 1 • Up to 5 years
Investigations Aspartate aminotransferase increased	5.3% 1/19 • Number of events 1 • Up to 5 years
Blood and lymphatic system disorders Febrile neutropenia	26.3% 5/19 • Number of events 9 • Up to 5 years
Blood and lymphatic system disorders Anemia	15.8% 3/19 • Number of events 3 • Up to 5 years
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	5.3% 1/19 • Number of events 2 • Up to 5 years
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	5.3% 1/19 • Number of events 4 • Up to 5 years
Gastrointestinal disorders Mucositis oral	21.1% 4/19 • Number of events 4 • Up to 5 years
Gastrointestinal disorders Diarrhea	15.8% 3/19 • Number of events 3 • Up to 5 years
Gastrointestinal disorders Nausea	15.8% 3/19 • Number of events 3 • Up to 5 years
Gastrointestinal disorders Vomiting	10.5% 2/19 • Number of events 2 • Up to 5 years
Gastrointestinal disorders Abdominal pain	5.3% 1/19 • Number of events 1 • Up to 5 years
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • Up to 5 years
Gastrointestinal disorders Enterocolitis	5.3% 1/19 • Number of events 1 • Up to 5 years
Infections and infestations Infections and infestations - Other	10.5% 2/19 • Number of events 2 • Up to 5 years
Infections and infestations Lung infection	5.3% 1/19 • Number of events 1 • Up to 5 years
General disorders Edema limbs	5.3% 1/19 • Number of events 1 • Up to 5 years
General disorders Infusion related reaction	5.3% 1/19 • Number of events 1 • Up to 5 years
Skin and subcutaneous tissue disorders Cellulitis	10.5% 2/19 • Number of events 2 • Up to 5 years
Skin and subcutaneous tissue disorders Rash maculo-papular	5.3% 1/19 • Number of events 1 • Up to 5 years

Additional Information

Charalambos Andreadis, MD, MSCE, Associate Professor of Clinical Medicine

University of California, San Francisco

Phone: 877-827-3222

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place