Trial Outcomes & Findings for Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder (NCT NCT04337827)

Last Updated: 2024-04-10

Results Overview

ORR will be estimated along with 90% Confidence Intervals (CIs), and compared against the null using exact binomial test. Logistic regression model will be used to identify factors associated with response status.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Up to 8 weeks after treatment

Results posted on

2024-04-10

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab and Acalabrutinib Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions. Rituximab: Weekly x 4 weeks. If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto Long Term Follow Up (LTFU). Acalabrutinib: 100mg twice per day (BID) x 4 weeks (28 day cycle) If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto LTFU. CT scans: 2 weeks (day 36 ± 5 days) after end of cycle 1 treatment.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab and Acalabrutinib n=6 Participants Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions. Rituximab: Weekly x 4 weeks. If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto Long Term Follow Up (LTFU). Acalabrutinib: 100mg twice per day (BID) x 4 weeks (28 day cycle) If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto LTFU. CT scans: 2 weeks (day 36 ± 5 days) after end of cycle 1 treatment.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 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	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 8 weeks after treatment

Population: Sponsor terminated financial support of all research activity not associated with active subjects receiving study medication enrolled under this IND, it has been decided to close enrollment and to cease long-term follow-up of subjects. Zero participants were followed past the end of treatment for several reasons, including removal of funding that prevented follow-up or participants reaching stable disease (per protocol, participant does not get followed). Therefore, no data was collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 6 months after treatment

Population: Due to notification by AstraZeneca to terminate financial support of all research activity not associated with active subjects receiving study medication enrolled under this IND, it has been decided to close the study to enrollment and to cease long-term follow-up of subjects not actively receiving study medication. Participants were unable to be followed after the end of treatment for 6 months; therefore, no data was collected.

CRR is defined as all patients that achieve a CR based on end of treatment scans, using the Lugano Criteria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 12 months after treatment

CRR is defined as all patients that achieve a CR based on end of treatment scans, using the Lugano Criteria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 24 months after treatment

CRR is defined as all patients that achieve a CR based on end of treatment scans, using the Lugano Criteria

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 6 months after treatment

PRR is defined as all patients that achieve a PR based on end of treatment scans, using the Lugano Criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 12 months after treatment

PRR is defined as all patients that achieve a PR based on end of treatment scans, using the Lugano Criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 24 months after treatment

PRR is defined as all patients that achieve a PR based on end of treatment scans, using the Lugano Criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years after treatment

DOR is only measured in responders. DOR is defined as the time from documented response (CR or PR) to the time of confirmed disease progression or death due to any cause, whichever occurs first. Subjects who are still alive and free from progression at the time of data cutoff date, lost to follow-up, have discontinued study, or have initiated other non-protocol anti-tumor therapy (NPT) will be censored at the last tumor assessment when subjects are progression-free.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 6 months after treatment

PFS as defined as the time from first dose to documented disease progression, or death from any cause, whichever occurs first. Data for subjects who are still alive and free from progression at the time of data cutoff date, lost to follow-up, have discontinued the study, or have initiated NPT will be censored on last assessment (or, if no post-baseline tumor assessment, at the time of first dose plus 1 day) Estimated using Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model will be used to identify factors associated with survival endpoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 12 months after treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at 24 months after treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years after treatment

Overall survival (OS) is defined as the time from first dose to death from any cause. Data for subjects who are still alive at the time of data cutoff date, lost to follow-up, have discontinued the study (or, if no post-baseline assessment, at the time of first dose plus 1 day) will be censored on last assessment Estimated using Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model will be used to identify factors associated with survival endpoint.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years after treatment

TTF is measured from the time from study entry to any treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years after treatment

Safety as defined by number of participants with a grade 3 AE or higher

Outcome measures

Outcome data not reported

Adverse Events

Rituximab and Acalabrutinib

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab and Acalabrutinib n=6 participants at risk Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions. Rituximab: Weekly x 4 weeks. If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto Long Term Follow Up (LTFU). Acalabrutinib: 100mg twice per day (BID) x 4 weeks (28 day cycle) If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto LTFU. CT scans: 2 weeks (day 36 ± 5 days) after end of cycle 1 treatment.
Infections and infestations Lung infection	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Respiratory, thoracic and mediastinal disorders Dyspnea	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).

Other adverse events

Other adverse events
Measure	Rituximab and Acalabrutinib n=6 participants at risk Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions. Rituximab: Weekly x 4 weeks. If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto Long Term Follow Up (LTFU). Acalabrutinib: 100mg twice per day (BID) x 4 weeks (28 day cycle) If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto LTFU. CT scans: 2 weeks (day 36 ± 5 days) after end of cycle 1 treatment.
Blood and lymphatic system disorders Anemia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Cardiac disorders Supraventricular tachycardia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Gastrointestinal disorders Abdominal pain	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Gastrointestinal disorders Anal hemorrhage	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Gastrointestinal disorders Constipation	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
General disorders Fatigue	50.0% 3/6 • Number of events 3 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
General disorders Fever	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Infections and infestations Infections and infestations	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Infections and infestations Lung infection	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Injury, poisoning and procedural complications Bruising	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Investigations Alkaline phosphatase increased	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Investigations Lymphocyte count decreased	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Investigations Neutrophil count decreased	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Investigations White blood cell decreased	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Metabolism and nutrition disorders Hyperglycemia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Metabolism and nutrition disorders Hypernatremia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Metabolism and nutrition disorders Hypoalbuminemia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Metabolism and nutrition disorders Hyponatremia	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Nervous system disorders Dizziness	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Nervous system disorders Headache	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Psychiatric disorders Insomnia	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Renal and urinary disorders Urinary Urgency	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Respiratory, thoracic and mediastinal disorders Dyspnea	33.3% 2/6 • Number of events 2 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Respiratory, thoracic and mediastinal disorders Sore throat	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).
Vascular disorders Hypertension	16.7% 1/6 • Number of events 1 • Adverse events were assessed on all subjects from the point of Eligibility Screening (baseline) to 30 days following the last dose of the study drug (which was 10 months on average).

Additional Information

Dr. Deepa Jagadeesh

Cleveland Clinic Foundation, Case Comprehensive Cancer Center

Phone: 1-866-223-8100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place