LCCC1841: A Phase 2 Trial of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas
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|ClinicalTrials.gov Identifier: NCT04548648|
Recruitment Status : Recruiting
First Posted : September 14, 2020
Last Update Posted : July 15, 2021
The purpose of this study is to see if acalabrutinib is effective in treating a type of cancer call central nervous system (CNS) lymphoma. Acalabrutinib has not been approved by the Food and Drug Administration (FDA) for the treatment of CNS lymphoma. However, FDA has approved its use for treatment of another type of lymphoma called mantle cell lymphoma. Currently, there are no standard FDA approved treatments for treatment of CNS lymphoma.
Acalabrutinib acts similar to another cancer drug called ibrutinib. Ibrutinib was tested in several research trials for management of CNS lymphomas, and the results were promising. Acalabrutinib and ibrutinib attack a similar target found in CNC lymphoma. Research studies show that acalabrutinib does a better job in attacking this target than ibrutinib, and this might be beneficial for using this drug in treating CNS lymphoma. The purpose of this study is test whether giving acalabrutinib is safe and could help controlling with CNS lymphoma. The study doctors will be looking to see if acalabrutinib can shrink the cancer.
In this research study, participants will be given acalabrutinib and isavuconazol, because it helps in preventing fungal infections. Fungal infection is a common side effect of acalabrutinib. Treatment with acalabrutinib and isavuconazole will continue unless the cancer progresses or participants experience bad side effects.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: Acalabrutinib Drug: Isavuconazole||Phase 2|
LCCC 1841 is a multicenter open-label, single-arm, phase 2 study designed to investigate the antitumor effects of acalabrutinib in subjects with relapsed primary central nervous system lymphoma (PCNSL), and relapsed secondary CNS lymphoma (SCNSL) with no evidence of current systemic disease. Subjects with the following histological subtypes of lymphoma will be included in the study: diffuse large B-cell lymphoma (DLBCL, all subtypes); mantle cell lymphoma (MCL, all subtypes); plasmablastic lymphoma, and lymphoplasmacytic lymphoma. Up to 32 subjects will receive acalabrutinib at the dose of 100 mg approximately every 12 hours. A Simon two-stage design will be used to minimize the expected sample size if the regimen has low activity. In the first stage, 15 evaluable subjects will be enrolled and treated. If =8 subjects have an overall response of stable disease or better as determined by the International Primary CNS Lymphoma Collaborative Group Response Assessment Criteria , an additional 13 subjects will be enrolled and treated in the second stage of the study for a total of 28 evaluable subjects treated on the trial. The study will accrue up to 32 subjects to ensure data from 28 evaluable subjects. If <8 subjects have an overall response of stable disease or better as determined by the International Primary CNS Lymphoma Collaborative Group Response Assessment Criteria, the study will be closed to accrual and no additional subjects will be enrolled. If the study shows a positive effect of acalabrutinib in treating CNS lymphomas, acalabrutinib could become the standard relapsed CNS lymphoma regimen, not only for PCNSL, but also in certain subtypes of SCNSL. Any complete responses to acalabrutinib treatment will be clinically notable as spontaneous remissions do not occur.
In a previous study, ibrutinib showed a CR rate of 45% and an ORR of 68% ; in another study ], ibrutinib showed a CR rate of 17% and an ORR of 55%. Thus, in order to recommend further investigation of acalabrutinib as a regimen for primary CNS lymphoma, acalabrutinib treatment must show an overall response rate (ORR) of at least 70%, which would demonstrate that it is not inferior to previously approved regimens.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||The study is designed as an open label, single arm phase II study to provide preliminary data about its efficacy before proceeding to a larger two arm study.|
|Masking:||None (Open Label)|
|Official Title:||LCCC1841: A Phase 2 Trial of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas|
|Estimated Study Start Date :||July 2021|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2028|
A multicenter open-label, single-arm, phase 2 study designed to investigate the antitumor effects of acalabrutinib in subjects with relapsed primary central nervous system lymphoma (PCNSL), and relapsed secondary CNS lymphoma (SCNSL) with no evidence of current systemic disease. Subjects will receive acalabrutinib at the dose of 100 mg every 12 hours. Prophylactic administration of broad spectrum triazole antifungal agent isavuconazole will be performed while subjects receive acalabrutinib.
Acalabrutinib at 100 mg is taken orally approximately every 12 hours until disease progression or unacceptable toxicity.
Prophylactic treatment with isavuconazole includes loading dose of 372 mg (2 capsules) administered orally every 8 hours for 6 doses (48 hours), followed by maintenance administration of 372 mg (2 capsules) once daily as long as the subject is on study treatment.
Other Name: Cresemba
- Overall response rate [ Time Frame: 2 years ]Overall response rate (ORR; ORR= Partial Response + Complete Response) will be assessed at 2 months as measured by the International Primary CNS Lymphoma Collaborative Group Response assessment criteria in subjects with relapsed/refractory primary and secondary CNS lymphoma receiving acalabrutinib.
- Number of different types of toxicities [ Time Frame: 3 years ]Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
- Progression-free survival (PFS) [ Time Frame: 5 years ]Progression-free survival (PFS) is defined from the date of initiating study treatment to the date of disease progression per the International Primary CNS Lymphoma Collaborative Group response assessment criteria or death as a result of any cause.
- Complete response (CR) rate [ Time Frame: 2 years ]Complete Response (CR) is defined using the International Primary CNS Lymphoma Collaborative Group response assessment criteria for primary CNS lymphoma.
- Duration of response (DoR) [ Time Frame: 2 years ]Duration of response (DoR) is defined as time from documentation of tumor response to disease progression according to the International Primary CNS Lymphoma Collaborative Group response assessment criteria.
- Overall Survival (OS) [ Time Frame: 5 years ]OS will be measured from the date of initiating study treatment to the date of death or 5 years (whichever is first). Subjects who have not died by the analysis data cut-off date will be censored at their last date of contact.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04548648
|Contact: Lynn Ruffin||9193081724||Lynn_ruffin@med.unc.edu|
|Contact: Jana Hallemail@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Christopher Dittus 919-966-4431 firstname.lastname@example.org|
|Contact: Jana Hall 9198433550 email@example.com|
|Levine Cancer Institute, Carolinas Health Care System||Not yet recruiting|
|Charlotte, North Carolina, United States, 28204|
|Principal Investigator: Nilanjan Ghosh, MD, PhD|
|Wake Forest University Comprehensive Cancer Center||Recruiting|
|Winston-Salem, North Carolina, United States, 27157-1096|
|Principal Investigator: David Hurd, MD|
|Principal Investigator:||Christopher Dittus||UNC Lineberger Comprehensive Cancer Center|