Trial Outcomes & Findings for Clinical Trial of Ublituximab and Umbralisib With CHOP (U2-CHOP) Followed by U2 Maintenance (U2-CHOP-U2) in Previously Untreated Mantle Cell Lymphoma (MCL) (NCT NCT04692155)

Results Overview

In the proposed study, the primary endpoint is to estimate the biological response rate of the combination of Umbralisib at dose 800 mg with Ublituximab (900mg)-CHOP, but a phase Ib portion with dose de-escalation at two does level (800 and 600 mg) will be built in to further confirm its safety and tolerability. Rate of complete remission at the end of induction treatment (U2-CHOP X 6 cycles) per PET/CT assessment criteria for Lymphoma (Cheson et al, 2014).Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

1 participants

Primary outcome timeframe

10 months

Results posted on

2023-09-28

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1b and Phase 2 for phase 1 B portion, Ublitixumab will be given IV at dosage 900mg from Cycle 1 Day1 till cycle 6. If investigator decides to continue the treatment as maintenance, Ublitixumab will be given IV every 8 weeks for 24 months Umbralisib (800mg) will be given orally once a day within 30 minutes of a meal from Cycle 1 Day1 till cycle 6.If investigator decides to continue the treatment as maintenance,• Umbralisib will be given at orally daily for 24 months. Chemotherapy combination of CHOP-cyclophosphamide IV 750mg/m2 for Age \<70 years, 500 mg/m2 for Age\>70 years doxorubicin IV 50mg/m2for Age \<70 years, 25 mg/m2 for Age\>70 years , and vincristine IV 1mg/m2 (max 2mg)) are administered on Cycle 1 day 1 till Cycle 6. Prednisone 50-100mg will be given orally on days 1 through 5 of every cycle. For Phase II portion- Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agrees. Ublituximab: Ublituximab (900mg) will be administered as an intravenous infusion through a dedicated line. Umbralisib: Umbralisib(800mg)will be administered orally once daily within 30 minutes of starting a meal.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b and Phase 2 for phase 1 B portion, Ublitixumab will be given IV at dosage 900mg from Cycle 1 Day1 till cycle 6. If investigator decides to continue the treatment as maintenance, Ublitixumab will be given IV every 8 weeks for 24 months Umbralisib (800mg) will be given orally once a day within 30 minutes of a meal from Cycle 1 Day1 till cycle 6.If investigator decides to continue the treatment as maintenance,• Umbralisib will be given at orally daily for 24 months. Chemotherapy combination of CHOP-cyclophosphamide IV 750mg/m2 for Age \<70 years, 500 mg/m2 for Age\>70 years doxorubicin IV 50mg/m2for Age \<70 years, 25 mg/m2 for Age\>70 years , and vincristine IV 1mg/m2 (max 2mg)) are administered on Cycle 1 day 1 till Cycle 6. Prednisone 50-100mg will be given orally on days 1 through 5 of every cycle. For Phase II portion- Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agrees. Ublituximab: Ublituximab (900mg) will be administered as an intravenous infusion through a dedicated line. Umbralisib: Umbralisib(800mg)will be administered orally once daily within 30 minutes of starting a meal.
Overall Study Death	1

Baseline Characteristics

Clinical Trial of Ublituximab and Umbralisib With CHOP (U2-CHOP) Followed by U2 Maintenance (U2-CHOP-U2) in Previously Untreated Mantle Cell Lymphoma (MCL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b and Phase 2 n=1 Participants for phase 1 B portion, Ublitixumab will be given IV at dosage 900mg from Cycle 1 Day1 till cycle 6. If investigator decides to continue the treatment as maintenance, Ublitixumab will be given IV every 8 weeks for 24 months Umbralisib (800mg) will be given orally once a day within 30 minutes of a meal from Cycle 1 Day1 till cycle 6.If investigator decides to continue the treatment as maintenance,• Umbralisib will be given at orally daily for 24 months. Chemotherapy combination of CHOP-cyclophosphamide IV 750mg/m2 for Age \<70 years, 500 mg/m2 for Age\>70 years doxorubicin IV 50mg/m2for Age \<70 years, 25 mg/m2 for Age\>70 years , and vincristine IV 1mg/m2 (max 2mg)) are administered on Cycle 1 day 1 till Cycle 6. Prednisone 50-100mg will be given orally on days 1 through 5 of every cycle. For Phase II portion- Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agrees. Ublituximab: Ublituximab (900mg) will be administered as an intravenous infusion through a dedicated line. Umbralisib: Umbralisib(800mg)will be administered orally once daily within 30 minutes of starting a meal.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 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	1 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

PRIMARY outcome

Timeframe: 10 months

Population: The patient died because of COVID infection. Not related to the study drug.

In the proposed study, the primary endpoint is to estimate the biological response rate of the combination of Umbralisib at dose 800 mg with Ublituximab (900mg)-CHOP, but a phase Ib portion with dose de-escalation at two does level (800 and 600 mg) will be built in to further confirm its safety and tolerability. Rate of complete remission at the end of induction treatment (U2-CHOP X 6 cycles) per PET/CT assessment criteria for Lymphoma (Cheson et al, 2014).Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Phase 1b and Phase 2 n=1 Participants for phase 1 B portion, Ublitixumab will be given IV at dosage 900mg from Cycle 1 Day1 till cycle 6. If investigator decides to continue the treatment as maintenance, Ublitixumab will be given IV every 8 weeks for 24 months Umbralisib (800mg) will be given orally once a day within 30 minutes of a meal from Cycle 1 Day1 till cycle 6.If investigator decides to continue the treatment as maintenance,• Umbralisib will be given at orally daily for 24 months. Chemotherapy combination of CHOP-cyclophosphamide IV 750mg/m2 for Age \<70 years, 500 mg/m2 for Age\>70 years doxorubicin IV 50mg/m2for Age \<70 years, 25 mg/m2 for Age\>70 years , and vincristine IV 1mg/m2 (max 2mg)) are administered on Cycle 1 day 1 till Cycle 6. Prednisone 50-100mg will be given orally on days 1 through 5 of every cycle. For Phase II portion- Once Umbralisib dose is defined in phase Ib, the study will expand to phase II portion after SMC/DSMB (Safety monitoring committee/Data Safety Monitoring Committee) agrees. Ublituximab: Ublituximab (900mg) will be administered as an intravenous infusion through a dedicated line. Umbralisib: Umbralisib(800mg)will be administered orally once daily within 30 minutes of starting a meal.
Rate of Complete Remission at the End of Induction Treatment	0 Participants

Adverse Events

Phase 1b and Phase 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Amitkumar Mehta

UAB

Phone: 2059968400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place