132 Participants Needed

Acalabrutinib + Chemotherapy for Non-Hodgkin's Lymphoma

NM
MJ
Overseen ByMark J Roschewski, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take medications that are moderate or strong CYP3A inhibitors or inducers, as these could interfere with the study drug.

What data supports the effectiveness of the drug Acalabrutinib in combination with chemotherapy for Non-Hodgkin's Lymphoma?

Acalabrutinib, a drug that blocks a protein important for cancer cell growth, has shown effectiveness in treating chronic lymphocytic leukemia (CLL) by significantly prolonging the time patients live without the disease getting worse. Additionally, combining Acalabrutinib with R-CHOP, a standard treatment for a type of Non-Hodgkin's Lymphoma, is being studied for its potential to improve treatment outcomes.12345

Is the combination of Acalabrutinib and chemotherapy safe for treating Non-Hodgkin's Lymphoma?

Acalabrutinib, when combined with chemotherapy regimens like R-CHOP, is being studied for safety in treating Non-Hodgkin's Lymphoma. Previous studies on Acalabrutinib for other conditions, such as chronic lymphocytic leukemia, have shown it to have an acceptable safety profile, with common side effects including headache, diarrhea, and infections. Serious side effects like high blood pressure and heart rhythm issues were less common.23467

How does the drug Acalabrutinib differ from other treatments for Non-Hodgkin's Lymphoma?

Acalabrutinib is a next-generation Bruton tyrosine kinase inhibitor that may offer improved potency and specificity, potentially leading to better efficacy and tolerability when combined with standard R-CHOP therapy for Non-Hodgkin's Lymphoma. This combination targets dysregulated B-cell receptor signaling, which is a feature of this type of lymphoma.23457

What is the purpose of this trial?

Background:Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. Most people with this cancer can be cured. But those who are not cured have a poor prognosis. Researchers want to add another drug to standard treatment see if it can improve the cure rate.Objective:To see if the drug acalabrutinib given with rituximab and standard combination chemotherapy can improve the cure rate of aggressive B-cell lymphomas such as diffuse large B-cell lymphoma.Eligibility:People ages 18 and older with an aggressive B-cell lymphomas that have not been treatedDesign:Participants will be screened with:Blood and urine testsPhysical examMedical historyTumor biopsyBone marrow biopsy: A needle will remove marrow from the participant s hipbone.Lumbar puncture: If necessary, a needle will remove fluid from the participant s spinal canal.Imaging scansParticipants will take the study drug for up to 14 days. It is a pill taken 2 times a day. Then they will have more scans. They will get rituximab and chemotherapy. They may get these drugs through a needle in an arm vein. Or they may them through a tube placed in a vein in their chest or in their neck. They might also keep taking the study drug. Each treatment cycle lasts 21 days. They will have up to 6 cycles.Participants may have 4 doses of another drug injected into their spinal fluid.Participants will have repeats of the screening tests throughout the study.Participants will have a follow-up visit 30 days after their last treatment, then every 3 months for 2 years, then every 6 months for 3 years, and then yearly.

Research Team

MJ

Mark J Roschewski, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18+ with untreated aggressive B-cell lymphomas, specifically diffuse large B-cell lymphoma or high-grade B-cell lymphoma. Participants must have measurable disease, adequate organ and marrow function, and be willing to use effective contraception. Pregnant women, those with CNS involvement by the cancer or certain other health conditions are excluded.

Inclusion Criteria

Effects of acalabrutinib on the developing human fetus are unknown. For these reasons the following measures apply: Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Women of childbearing potential (WOCBP) who are sexually active must agree to highly-effective contraception prior to study entry, for the duration of study participation, and for at least 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Male subjects must use highly effective contraception prior to study entry, for the duration of study participation, and for 12 months after the last dose of combined chemotherapy; there is no contraception timing requirement post-last dose of acalabrutinib alone if male subject does not initiate chemotherapy on study after the acalabrutinib window. Participants must not be planning to conceive or father children within the projected duration of the trial, starting with the pre-screening/screening visit through 2 days after the last dose of acalabrutinib or 12 months after the last dose of combined chemotherapy, whichever is later. Ability of patient to understand and the willingness to sign a written informed consent document. Any HIV status will be included in this study; status must be confirmed prior to enrollment.
I have an aggressive type of B-cell lymphoma and have not been treated for it.
I can provide a tumor sample for study, or I'm willing to have a biopsy if needed.
See 4 more

Exclusion Criteria

I do not have an active hepatitis B infection or a positive hepatitis B PCR test.
I do not have any other cancer requiring ongoing treatment.
My lymphoma has spread to my brain or spinal cord.
See 18 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
Multiple visits for tests and biopsies

Initial Treatment

Participants receive acalabrutinib for 14 days to assess initial response

2 weeks
1 visit for drug administration and assessment

Chemoimmunotherapy

Participants receive R-CHOP or DA-EPOCH-R, with or without acalabrutinib, based on initial response

18 weeks
6 cycles of 21 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years
Every 3 months for 2 years, then every 6 months for 3 years, then yearly

Treatment Details

Interventions

  • Acalabrutinib
  • CHOP
  • DA-EPOCH
  • Rituximab
Trial Overview The trial is testing if adding acalabrutinib (a pill) to standard chemotherapy regimens (DA-EPOCH-R or R-CHOP) along with rituximab improves cure rates in aggressive B-cell lymphomas like diffuse large B-cell lymphoma. The treatment includes up to six cycles of therapy lasting 21 days each.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 1Experimental Treatment4 Interventions
Acalabrutinib 100 mg orally twice a day for 14 days; Following window: patients with \> or = to 25% tumor reduction, treat with DA-EPOCH-R or R-CHOP + acalabrutinib 100mg orally twice a day for the first 10 days, for 6 cycles; whereas, patients with \<25% tumor reduction, treat with DA-EPOCH-R or R-CHOP alone for 6 cycles

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 29 patients with advanced diffuse histiocytic lymphoma, the CHOP-B chemotherapy regimen resulted in a higher complete response rate of 87% compared to 64% for the ACOMLA regimen, indicating better efficacy for CHOP-B.
Despite the higher response rate with CHOP-B, both treatments had significant toxicity, including nonfatal sepsis and drug-related deaths, highlighting the need for careful monitoring during chemotherapy.
Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma.Newcomer, LN., Cadman, EC., Nerenberg, MI., et al.[2015]
The ACCEPT trial is investigating the safety and efficacy of adding acalabrutinib, a second-generation Btk inhibitor, to the standard R-CHOP regimen in patients with untreated Diffuse Large B-cell Lymphoma (DLBCL), with a focus on establishing the recommended dose and assessing overall response rates.
This open-label trial includes up to 39 participants and aims to provide preliminary evidence on the combination's effectiveness and safety, potentially paving the way for larger Phase II/III trials in the future.
ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial.Davies, A., Barrans, S., Burton, C., et al.[2021]
Acalabrutinib has been approved in the EU for treating both treatment-naïve and relapsed/refractory chronic lymphocytic leukemia (CLL), showing significant improvements in progression-free survival compared to standard therapies in two phase III trials involving adult patients.
The safety profile of acalabrutinib is generally acceptable, with common side effects including headache, diarrhea, and infections, and the overall benefit-risk ratio is considered positive for its use in CLL.
EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia.Delgado, J., Josephson, F., Camarero, J., et al.[2021]

References

Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. [2015]
ACCEPT - combining acalabrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) for Diffuse Large B-cell Lymphoma (DLBCL): study protocol for a Phase Ib/II open-label non-randomised clinical trial. [2021]
EMA Review of Acalabrutinib for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia. [2021]
Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. [2022]
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]
Acalabrutinib in treatment-naive chronic lymphocytic leukemia. [2022]
Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]
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