A Pilot Study 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 : March 25, 2022
The purpose of this study is to test whether giving acalabrutinib is safe and effective in controlling relapsed central nervous system (CNS) lymphoma. Currently, there are no FDA-approved treatments for relapsed CNS lymphoma. Although acalabrutinib has not been approved for the treatment of CNS lymphoma, it was approved for the treatment of another type of lymphoma (mantle cell), by the Food and Drug Administration (FDA).
Acalabrutinib acts similar to another cancer drug called ibrutinib. lbrutinib was tested in several research trials for the management of CNS lymphomas, and the results were promising. Acalabrutinib and ibrutinib attack a similar target found in CNS lymphoma. Acalabrutinib may do a better job in attacking this target than ibrutinib. The study doctors will be looking to see if acalabrutinib can shrink cancer cells.
The participants will be given acalabrutinib and isavuconazole, because isavuconazole helps in preventing fungal infections that may occur during acalabrutinib treatment.
|Condition or disease||Intervention/treatment||Phase|
|Central Nervous System Lymphoma||Drug: Acalabrutinib Drug: Isavuconazole||Phase 2|
This multicenter open-label, single-arm, pilot study explores a safe and effective treatment for relapsed central nervous system lymphoma. The study investigates the antitumor effects and safety of acalabrutinib in subjects with relapsed primary central nervous system lymphoma (PCNSL) or relapsed secondary CNS lymphoma (SCNSL) with no evidence of current systemic disease. Types of SCNSL included in the study are: Diffuse large B-cell lymphoma, mantle cell lymphoma, plasmablastic lymphoma, and lymphoplasmacytic lymphoma. Up to 16 subjects will be enrolled to attain a total of 15 evaluable subjects.
Duration of Therapy: Treatment with acalabrutinib and isavuconazole will continue unless
- Disease progression
- Inter-current illness that prevents further administration of treatment
- Unacceptable adverse event(s)
- Subject decides to withdraw from study treatment,
- General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator, or
- Subject is lost to follow up
Duration of Follow-up All subjects will be followed for survival for 5 years or until death, whichever occurs first.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Simon Two-stage study to a pilot study.|
|Masking:||None (Open Label)|
|Official Title:||LCCC1841: A Pilot Study of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas|
|Actual Study Start Date :||October 15, 2020|
|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 months ]
Overall response rate (ORR) will be assessed 2 months after receiving acalabrutinib as measured by the International Primary CNS Lymphoma Collaborative Group Response assessment criteria. Responder = Partial Response + Complete Response).
Complete response (CR) as complete disappearance of contrast enhancement on magnetic resonance imaging (MRI), no evidence of ocular lymphoma, negative cerebrospinal fluid (CSF) cytology, and discontinuation of corticosteroid use for at least 2 weeks prior to the evaluation of response. Unconfirmed CR (Cru) is used to characterize radiographic findings that fulfill criteria for a CR, but the patient remains on corticosteroids, or MRI that continues to show small but persistent enhancing abnormalities possibly related to biopsy or surgery. Partial response (PR) is defined as a 50% decrease in enhancing tumor or residual disease on eye examinations, or persistent or suspicious CSF cytology.
- 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 Hallfirstname.lastname@example.org|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Christopher Dittus 919-966-4431 email@example.com|
|Contact: Jana Hall 9198433550 firstname.lastname@example.org|
|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|