Trial Outcomes & Findings for Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies (NCT NCT02483000)

Results Overview

Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

Up to 30 days after transplant

Results posted on

2020-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (PRIT) B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (PRIT) n=3 Participants B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	58 Years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic	3 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days after transplant

Population: This outcome measure was not done. The starting dose level was level 1 (30 mCi/m2) and in the first stage, up to two patients would be treated at escalating doses in 20 mCi/m2 increments until a DLT was observed. With the 3 participants enrolled, only dose level 5 of 12 was achieved before the study was closed early. The Maximum Tolerated Dose was not determined due to small sample size.

Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 days after infusion

Population: Absorbed dose in target organs.

Assessed using OLINDA dosimetry software. The estimated dose to normal organs and tumor sites will be described based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 DOTA-biotin.

Outcome measures

Outcome measures
Measure	Treatment (PRIT) n=3 Participants B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Dosimetry of Yttrium Y 90 DOTA-biotin Liver	2.5 cGy/mCi Interval 1.83 to 2.61
Dosimetry of Yttrium Y 90 DOTA-biotin Spleen	3.73 cGy/mCi Interval 2.4 to 4.17
Dosimetry of Yttrium Y 90 DOTA-biotin Lungs	0.229 cGy/mCi Interval 0.194 to 0.477
Dosimetry of Yttrium Y 90 DOTA-biotin Kidneys	11.4 cGy/mCi Interval 5.57 to 11.9
Dosimetry of Yttrium Y 90 DOTA-biotin Bone Marrow	3.75 cGy/mCi Interval 1.73 to 5.96
Dosimetry of Yttrium Y 90 DOTA-biotin Brain	0.229 cGy/mCi Interval 0.194 to 0.477

SECONDARY outcome

Timeframe: Up to 30 days after transplant

Descriptive statistics on the number and percent toxicities will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (PRIT) n=3 Participants B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Serious Adverse Events	2 Participants
Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Other (Not Including Serious) Adverse Events	2 Participants

SECONDARY outcome

Timeframe: Up to 4 years

Descriptive statistics on the responses will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (PRIT) n=3 Participants B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Overall Response Rate Participants who achieved a CR	2 Participants
Overall Response Rate Participants who achieved a PR	1 Participants

SECONDARY outcome

Timeframe: Up to 4 years

Overall survival will be estimated.

Outcome measures

Outcome measures
Measure	Treatment (PRIT) n=3 Participants B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Overall Survival	2 Participants

SECONDARY outcome

Timeframe: 1 year from autologous stem cell transplant

Population: This outcome measure was not done since 24 patients were needed to provide 80% power to detect statistical significance. The sample size of 3 patients is too small to determine the true 1-year PFS rate.

If the true 1-year PFS rate using the proposed approach is 54%, then 24 patients will provide 80% power to detect a statistically significant increased rate of PFS from the fixed rate of 30%, based on a one-sample chi-square test with one-sided significance level of 5%.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (PRIT)

Serious events: 2 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (PRIT) n=3 participants at risk B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.
Blood and lymphatic system disorders Febrile Neutropenia	66.7% 2/3 • Number of events 2 • AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.
Gastrointestinal disorders Mucositis, Oral	66.7% 2/3 • Number of events 2 • AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.

Other adverse events

Other adverse events
Measure	Treatment (PRIT) n=3 participants at risk B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.

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