Acalabrutinib + Anti-CD20 + Venetoclax for Chronic Lymphocytic Leukemia

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Acerta Pharma BV

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

To evaluate the safety and preliminary efficacy of acalabrutinib in combination with obinutuzumab in 4 separate cohorts of participants.

Research Team

AstraZeneca Study Information Center

Principal Investigator

1-877-240-9479; information.center@astrazeneca.com

Eligibility Criteria

This trial is for adults with certain types of leukemia and lymphoma, including CLL/SLL/PLL. Participants can be treatment-experienced or untreated, depending on the cohort they qualify for. They must have adequate organ function, not be pregnant or breastfeeding, agree to contraception if applicable, and cannot have secondary cancers affecting life expectancy or confounding factors.

Inclusion Criteria

Participant must provide written informed consent

My organs work well, I don't have another cancer, and my doctor thinks I'll live more than 2 years.

I am 18 years old or older.

See 7 more

Exclusion Criteria

I have received treatment for CLL before.

I have heart disease or a long QT interval.

I do not have HIV, hepatitis B or C, or any uncontrolled infections.

See 15 more

Treatment Details

Interventions

Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor)
Obinutuzumab (Monoclonal Antibodies)
Rituximab (Monoclonal Antibodies)
Venetoclax (B-cell Lymphoma-2 (BCL-2) Inhibitor)

Trial OverviewThe safety and efficacy of acalabrutinib combined with obinutuzumab are being tested in four cohorts of participants with different disease statuses (treated/untreated). The study will assess how well this combination works for those who meet specific health criteria.

Participant Groups

4Treatment groups

Experimental Treatment

Group I: Cohort 4: Acalabrutinib+Obinutuzumab+Venetoclax (Treatment-naive)Experimental Treatment3 Interventions

The treatment-naïve participants with CLL will receive oral acalabrutinib, IV infusion of obinutuzumab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive obinutuzumab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, Dose 2 on Cycle 2 Day 2, Dose 3 on Cycle 2 Days 8 and 15, and Dose 3 on Day 1 of Cycles 3 to 7. Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15 as Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and from Cycle 4 Day 1 participants will receive Dose 5 QD until completion of Cycle 15.

Group II: Cohort 3: Acalabrutinib+Rituximab+Venetoclax (R/R)Experimental Treatment3 Interventions

The R/R participants with CLL will receive oral acalabrutinib, IV infusion of rituximab, and oral venetoclax. Participants will receive acalabrutinib Dose 2 BID in 28-day continuous cycles until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first. Participants will receive rituximab for total 6 cycles (from Cycles 2 to 7) as Dose 1 on Cycle 2 Day 1, followed by Dose 1 every 3 weeks (Q3W) for 3 doses, then every 4 weeks (Q4W) for 5 doses (total 9 infusions through the end of Cycle 7). Participants will receive venetoclax weekly ramp-up schedule over 5 weeks from Cycles 3 to 15, Dose 1 QD for 1 week on Cycle 3 Day 1, Dose 2 QD for 1 week on Cycle 3 Day 8, Dose 3 QD for 1 week on Cycle 3 Day 15, Dose 4 QD for 1 week on Cycle 3 Day 22, and Dose 5 QD from Cycle 4 Day 1 until completion of Cycle 15.

Group III: Cohort 2: Acalabrutinib+Obinutuzumab (Treatment-naive)Experimental Treatment2 Interventions

Dose-escalation and dose-expansion phases will be conducted for treatment-naïve participants with CLL/ small lymphocytic lymphoma (SLL). In dose-escalation phase, participants will receive oral acalabrutinib Dose 2 BID in first cycle (28-day cycle). In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive IV infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

Group IV: Cohort 1: Acalabrutinib+Obinutuzumab (R/R)Experimental Treatment2 Interventions

Dose-escalation and dose-expansion phases will be conducted for relapsed/refractory (R/R) participants with CLL. In dose-escalation phase, participants will receive oral acalabrutinib Dose 1 once daily (QD), later the dose was switched to Dose 2 twice daily (BID) per Amendment 02. In dose- expansion phase, participants will receive oral acalabrutinib Dose 2 BID in 28-day continuous cycles; and will receive intravenous (IV) infusion of obinutuzumab for total 6 cycles (from Cycles 2 to 7) as on Cycle 2 Day 1 participants will receive Dose 1, on Cycle 2 Day 2 participants will receive Dose 2, on Cycle 2 Days 8 and 15 participants will receive Dose 3, and on Day 1 of Cycles 3 to 7 participants will receive Dose 3. Participants will continue to receive acalabrutinib Dose 2 BID until disease progression, an unacceptable drug-related toxicity, or per the investigator the study treatment is intolerable or no longer in participant's best interest, whichever occurs first.

Acalabrutinib is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Calquence for: