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Clinical Trial 21634

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04548648

Phase: Phase I
Principal Investigator: Bello, Celeste

Call 813-745-6100
or 1-800-679-0775 Learn More

Overview

Study Title

A Pilot Study of Acalabrutinib in Relapsed/Refractory Primary and Secondary CNS Lymphomas

Summary

The purpose of this study is to test whether giving acalabrutinib is safe and effective in controlling relapsed central nervous system (CNS) lymphoma

Objective

1. Determine overall response rate (ORR) in subjects with relapsed/refractory primary and secondary CNS lymphoma receiving acalabrutinib; 2. Assess toxicity of acalabrutinib in subjects with relapsed/refractory primary and secondary CNS lymphoma; 3. Determine clinical activity of acalabrutinib in subjects with relapsed/refractory primary and secondary CNS lymphoma by assessment of the median progression free survival (PFS); 4. Determine the complete response (CR) rate of acalabrutinib for the treatment of relapsed/refractory primary and secondary CNS lymphoma; 5. Determine duration of response (DoR) in subjects with relapsed/refractory primary and secondary CNS lymphoma receiving acalabrutinib; 6. Determine overall survival (OS) in subjects with relapsed/refractory primary and secondary CNS lymphoma receiving acalabrutinib.

Treatments

Therapies

Therapy (NOS)

Medications

ACP-196 (Acalabrutinib); Acalabrutinib (); Isavuconazole ()

Inclusion Criteria

Inclusion Criteria:

Willing and able to participate in all required evaluations and procedures in this study protocol, including swallowing capsules and tablets without difficulty.

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

Age ≥18 years at the time of consent.

Has adequate performance status as defined by The Eastern Cooperative Oncology Group (ECOG) of ≤ 2. (Note: Performance status can be assessed after administration of corticosteroids.)

Has histological confirmation of biopsy-proven CNS lymphoma OR MRI findings consistent with CNS lymphoma if biopsy is not possible (due to inaccessible location). Subjects with intra-ocular lymphoma will not be excluded as long as there is also parenchymal disease.

Has B-cell Non-Hodgkin Lymphoma.

Has no evidence of systemic involvement of lymphoma confirmed by CT or PET-CT imaging within 28 days prior to first dosing in the study.

Must have received at least one prior line of chemotherapy for primary or secondary CNS lymphoma. There is no limit on the number of prior treatment regimens.

Has adequate organ function as demonstrated by: System Laboratory Value Hematological* Absolute Neutrophil Count (ANC) ≥ 1 x 109/L Platelets ≥ 75 x 109/L Renal* Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula (Appendix B) Hepatic* Bilirubin ≤ 1.5 × upper limit of normal (ULN). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is > Is able to receive isavuconazole for prophylaxis of invasive aspergillosis while subject receives acalabrutinib therapy.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Female patients of childbearing potential must have a negative serum pregnancy test within three days (72 hours) prior to initiating study treatment. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 2 days after the last dose of acalabrutinib. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.

Other criteria may apply

Exclusion Criteria

Exclusion Criteria:

Patients meeting any of the following exclusion criteria will not be able to participate in this study 2.Prior cancer treatment that was completed less than 14 days prior to Day 1 of study dosing or if subject has not recovered from all reversible acute toxic effects of the regimen to grade ≤1 or baseline.

Prior brain radiotherapy under the following conditions: Whole-brain radiotherapy (WBRT) that was completed less than 28 days prior to Day 1 of study dosing Stereotactic radiosurgery (SRS) that was competed less than 14 days prior to Day 1 of study dosing.

Currently participating in or has participated in a study of an investigational agent within 28 days of first dosing with study treatment.

Is pregnant or breastfeeding.

Has active cerebrospinal fluid (CSF) involvement that requires ongoing intrathecal chemotherapy.

Previous exposure to a Bruton Tyrosine Kinase (BTK) inhibitor. 7. Subjects with severe hepatic insufficiency, as defined by Child-Pugh Score > 6.

Is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy.

Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 14 days of first dose of study drug. Subjects requires or is taking direct oral anticoagulants within 7 days of first dose of study drug.

Requires treatment with proton pump inhibitors. Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.

Is currently receiving any chemotherapy, anticancer immunotherapy. 12. Subject has clinically significant cardiovascular disease such as ventricular dysfunction, symptomatic coronary artery disease, uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification at screening. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.

Has familial short QT syndrome. 14. Subject has a history of malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass that is likely to affect absorption.

Has a known history of infection with HIV or any uncontrolled active significant infection.

Has a known history of drug-specific hypersensitivity or anaphylaxis to acalabrutinib or isavuconazole.

Has active bleeding or history of bleeding diathesis. 18. Subject has a history of uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).

Has a history of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of acalabrutinib.

Had major surgical procedure within 28 days of first dose of acalabrutinib.

Patients who are hepatitis B core antibody (anti-HBc) positive and who are hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR result before randomization and must be willing to undergo DNA PCR testing during the study. Subjects who are core antibody positive and viral load negative must receive entecavir Those who are HbsAg-positive, or hepatitis B PCR positive will be excluded.

Patients who are hepatitis C antibody positive must have a negative polymerase chain reaction (PCR) result. Those who are hepatitis C PCR positive will be excluded.

Other criteria apply

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