Acalabrutinib + Lenalidomide + Rituximab for Mantle Cell Lymphoma

Overseen By Rita Vaccaro, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Aspirin, Antivirals

Must not be taking: CYP3A4 inhibitors, Warfarin

Disqualifiers: Blastoid histology, CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for patients with untreated mantle cell lymphoma. The treatment aims to stop cancer growth, help the immune system fight the cancer, and directly target and kill the cancer cells.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as strong CYP3A4 inhibitors/inducers and proton pump inhibitors, before starting the study drugs. If you are on moderate CYP3A inhibitors, you may need a 7-day washout period (time without taking these medications) before joining the trial.

What data supports the effectiveness of the drug combination Acalabrutinib, Lenalidomide, and Rituximab for treating Mantle Cell Lymphoma?

Acalabrutinib has received accelerated approval for mantle cell lymphoma based on a phase II study, and the combination of lenalidomide and rituximab has shown promise in treating this condition. Additionally, a study combining rituximab, lenalidomide, and a similar drug, ibrutinib, showed high response rates in patients with relapsed or refractory mantle cell lymphoma. ^{1 2 3 4 5}

Is the combination of Acalabrutinib, Lenalidomide, and Rituximab safe for humans?

Acalabrutinib, Lenalidomide, and Rituximab have been studied for safety in treating mantle cell lymphoma. Acalabrutinib is generally well-tolerated, but treatment-related side effects can affect adherence. Lenalidomide and Rituximab have been tested together to find the safest dose, showing promise in safety and effectiveness for relapsed or refractory mantle cell lymphoma. ^{1 2 4 6 7}

What makes the drug combination of Acalabrutinib, Lenalidomide, and Rituximab unique for treating mantle cell lymphoma?

This drug combination is unique because it includes Acalabrutinib, a Bruton's tyrosine kinase inhibitor, which has shown promise in treating mantle cell lymphoma by targeting specific pathways in cancer cells. When combined with Lenalidomide and Rituximab, it offers a novel approach that may enhance efficacy compared to other regimens, potentially improving outcomes for patients with this challenging condition. ^{1 2 3 5 8}

Research Team

Jia Ruan, M.D., Ph.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for adults with untreated mantle cell lymphoma who need treatment, have good liver and kidney function, can follow the study schedule, and agree to use birth control. People with certain heart conditions, active infections like HIV or hepatitis B/C, recent major surgery, other cancers within 5 years (except some skin or localized cancers), or those on specific medications are excluded.

Inclusion Criteria

Understand and voluntarily sign an ICF prior to any study related assessments and procedures are conducted

I am registered and can follow the Revlimid REMS program.

I can take care of myself and do some daily activities.

Exclusion Criteria

I have a condition that affects how my body absorbs food.

I am at high risk for blood clots and refuse to take preventive medication.

I do not have a bleeding disorder like hemophilia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive 12 cycles of acalabrutinib, lenalidomide, and rituximab (ALR) treatment

12 months

Monthly visits for each cycle

Maintenance

Responding subjects continue maintenance ALR until disease progression, unacceptable toxicity, or withdrawal

Until disease progression or withdrawal

Follow-up

Participants are monitored every 6 months for alternate anti-cancer therapy and survival

4 years

Biannual visits

Treatment Details

Interventions

• Acalabrutinib
• Lenalidomide
• Rituximab

Trial Overview The trial tests a combination of acalabrutinib, lenalidomide and rituximab (ALR) in patients with untreated mantle cell lymphoma over an induction phase of 12 cycles followed by maintenance therapy until disease progression or unacceptable side effects occur. The effectiveness and safety of this regimen will be monitored throughout the study.

Participant Groups

Group I: ALR in Combination Experimental Treatment 3 Interventions

Acalabrutinib, lenalidomide, and rituximab in combination

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

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Celgene Corporation

Industry Sponsor

Trials

446

Recruited

58,500+

Mark Alles

Celgene Corporation

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Sol J. Barer

Celgene Corporation

Chief Medical Officer since 2006

PhD in Organic and Physical Chemistry from Rutgers University

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Acalabrutinib (Calquence®) has received accelerated approval from the US FDA for treating mantle cell lymphoma, based on promising results from a phase II study.

Phase III trials are currently ongoing for acalabrutinib in mantle cell lymphoma and chronic lymphocytic leukaemia, indicating its potential for broader application in treating hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. Markham, A., Dhillon, S.[2018]

The maximum tolerated dose (MTD) of lenalidomide when combined with rituximab for treating relapsed or refractory mantle-cell lymphoma (MCL) was determined to be 20 mg, with the combination showing a manageable safety profile despite some grade 3-4 hematological toxicities.

In a phase 2 trial involving 44 patients, the combination therapy resulted in a 57% overall response rate, with 36% achieving a complete response and a median overall survival of 24.3 months, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Wang, M., Fayad, L., Wagner-Bartak, N., et al.[2023]

Acalabrutinib demonstrated significantly higher overall response rates (ORR) and complete response (CR) rates compared to other targeted therapies for relapsed/refractory mantle cell lymphoma (MCL), indicating its efficacy in treating this condition.

The safety profile of acalabrutinib was comparable or better than that of other monotherapies, although it did show increased risks of infection and anemia compared to certain combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Telford, C., Kabadi, SM., Abhyankar, S., et al.[2021]

In a phase 2 trial involving 50 patients with relapsed or refractory mantle cell lymphoma, the combination of ibrutinib, lenalidomide, and rituximab resulted in a high overall response rate of 76%, with 56% achieving a complete response, suggesting this triplet therapy is effective.

While the treatment showed promising efficacy, it was associated with significant adverse events, including neutropenia in 38% of patients and three treatment-related deaths, highlighting the need for careful monitoring and further evaluation in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. Jerkeman, M., Eskelund, CW., Hutchings, M., et al.[2022]

In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.

Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. Badillo, M., Nava, D., Rosa, M., et al.[2022]

Bruton's tyrosine kinase inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective and well-tolerated treatment options for patients with mantle cell lymphoma who have already undergone one line of therapy.

These inhibitors offer a promising alternative for patients who experience relapse or drug resistance after initial chemo-immunotherapy, highlighting the need for novel treatment strategies in this aggressive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. Hanna, KS., Campbell, M., Husak, A., et al.[2021]

In a study of 20 patients with mantle cell lymphoma (MCL), the combination of rituximab and chlorambucil (R-Chl) achieved a high overall response rate of 95%, with 90% of patients reaching complete remission (CR).

The treatment resulted in a 3-year progression-free survival rate of 89% and was well-tolerated, with no serious side effects reported, making it a promising first-line option for patients with indolent disease features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Sachanas, S., Pangalis, GA., Vassilakopoulos, TP., et al.[2019]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]

7. England pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. [2019]