Trial Outcomes & Findings for Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies (NCT NCT01921387)

NCT ID: NCT01921387

Last Updated: 2020-08-04

Results Overview

Single patients will be treated at escalating doses in 2-Gy increments (Table 4) until a DLT is observed. Once a DLT is observed, the second stage will begin at the next lower dose level and patients will be treated in cohorts of 4.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Within 30 days post-transplant

Results posted on

2020-08-04

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Overall Study STARTED	20
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Overall Study Adverse Event	1

Baseline Characteristics

Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=20 Participants Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 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	0 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	17 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 days post-transplant

Outcome measures

Outcome measures
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=19 Participants Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA	34 Gy - MTD

PRIMARY outcome

Timeframe: 1 year

Estimate the 1 year progression-free survival (PFS) rate after ASCT

Outcome measures

Outcome measures
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=19 Participants Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Progression-free Survival Following Autologous Stem Cell Transplant (ASCT)	12 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Will be evaluated among all patients and among those treated at the estimated MTD.

Outcome measures

Outcome measures
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=19 Participants Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Estimated Dose to Tumor Sites 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 Anti-CD45 Monoclonal Antibody BC8	52.8 mCi

SECONDARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=19 Participants Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients	0.75 mg/kg

Adverse Events

Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC)

Serious events: 20 serious events

Other events: 0 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (90Y-BC8-DOTA, Chemotherapy, PBSC) n=20 participants at risk Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0. Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant Carmustine: Given IV Cytarabine: Given IV Etoposide: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Peripheral Blood Stem Cell Transplantation: Undergo autologous PBSC transplant Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8: Given IV
Immune system disorders Allergic reaction	15.0% 3/20 • Number of events 3 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Immune system disorders Anaphylaxis	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Metabolism and nutrition disorders Anorexia	25.0% 5/20 • Number of events 5 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Cardiac disorders Chest pain	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Respiratory, thoracic and mediastinal disorders Cough	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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 Diarrhea	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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	65.0% 13/20 • Number of events 13 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
General disorders Fever	15.0% 3/20 • Number of events 3 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Nervous system disorders Headache	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Metabolism and nutrition disorders Hyponatremia	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Metabolism and nutrition disorders Hypophosphatemia	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Vascular disorders Hypotension	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Immune system disorders Engraftment syndrome	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Infections and infestations Blood infection	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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	75.0% 15/20 • Number of events 15 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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 Nausea	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Nervous system disorders Peripheral neuropathy	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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	15.0% 3/20 • Number of events 3 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Immune system disorders Serum sickness	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Infections and infestations Sinusitis	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; Beyond day 30 after transplant/discharge from the transplant service until day 100, only SAEs and grade 4 and 5 toxicities will be collected.
Nervous system disorders Syncope	10.0% 2/20 • Number of events 2 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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 Vomiting	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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 Pruritus	5.0% 1/20 • Number of events 1 • AEs are monitored and recorded from the time of first exposure to the investigational agent (i.e., the start of the 111In-DOTA-BC8 infusion) through day +30 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician; 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

Adverse event data not reported

Additional Information

Ajay Kumar Gopal, MD, Director of Clinical Research

Seattle Cancer Care Alliance

Phone: (206) 606-2037

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place