Phase II Study of Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder (PTLD)
Overview
- Phase
- Phase 2
- Intervention
- Rituximab
- Conditions
- Post-transplant Lymphoproliferative Disorder
- Sponsor
- Deepa Jagadeesh
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to evaluate how effective rituximab and acalabrutinib are when given as a combination treatment for newly diagnosed B cell post transplant lymphoproliferative disorder (PTLD). Currently there is no approved therapy for PTLD. Rituximab alone is commonly used and works in some cases, but not others. In addition, participants with PTLD have trouble tolerating therapies with large amounts of side effects due to their health conditions and medications for their transplant. Due to these reasons the study team is looking for a new treatment with novel targeted agents in order to improve outcomes and to minimize toxicity.
Based on emerging data of clinical efficacy of acalabrutinib in B cell malignancies and an unmet need for novel therapies in PTLD, this study will investigate the use of rituximab and acalabrutinib in participants with newly diagnosed B cell PTLD.
Detailed Description
This is a non-randomized phase II study of acalabrutinib plus rituximab in newly diagnosed B-cell PTLD in participants with both solid organ transplant (SOT) and Bone marrow transplant (BMT). Acalabrutinib is an inhibitor of Bruton Tyrosine Kinase (BTK). BTK is important in B cells and plays a role in the development of PTLD. Acalabrutinib is approved in the US for the treatment of adult participants with indolent lymphoma, mantle cell lymphoma, and is being evaluated to treat other lymphomas. Rituximab has been approved for treatment of B cell non-Hodgkin lymphoma (NHL). While not approved for PTLD, it has become the mainstay of treatment. The primary objective of this study is to determine the overall response rate to combination treatment with rituximab and acalabrutinib in patients with PTLD. The secondary objectives of this study is to determine response rates, survival, failure rates, and safety elements in participants with PTLD treated with combination rituximab and acalabrutinib.
Investigators
Deepa Jagadeesh
Principal Investigator
Case Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Subjects must have a biopsy confirmed newly diagnosed CD20 positive B cell PTLD.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •ECOG 3 will be permitted if the decline in performance status is due to lymphoma. \[See Appendix 1\]
- •Subjects must have adequate hematologic, hepatic, and renal function as defined below:
- •Hemoglobin ≥ 8 gm/dL
- •Absolute neutrophil count ≥500/mcL (unless documented bone marrow involvement with lymphoma)
- •Platelet count ≥50000/mcL (unless there is documented bone marrow involvement with lymphoma)
- •Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of Lupus anticoagulant) \< 2x ULN.
- •Total bilirubin ≤1.5X upper limit of normal (ULN)
- •Creatinine ≤2.5X upper limit of normal (ULN)
Exclusion Criteria
- •Prior treatment with any BTK inhibitor
- •Subjects receiving any other investigational agents or participating in another therapeutic clinical trial.
- •Subjects with active (treated or untreated) brain metastases/ central nervous system (CNS) disease (including but not limited to CNS PTLD) will be excluded from this clinical trial
- •Prior malignancy (or any other malignancy that requires active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, early stage prostate cancer or other cancer from which the subject has been disease free for ≥ 3 years
- •Clinically significant cardiovascular disease such as 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 Functional Classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll in the study.
- •Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication.
- •Known history of infection with HIV. HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with acalabrutinib.
- •Patients with uncontrolled concurrent illness like active infection (eg, bacterial, viral, or fungal) requiring IV antibiotics or psychiatric illness/social situations that would limit compliance with study requirements
- •Known history of drug-specific hypersensitivity or anaphylaxis to acalabrutinib or rituximab (including active product or excipient components).
- •Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
Arms & Interventions
Rituximab and Acalabrutinib
Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions.
Intervention: Rituximab
Rituximab and Acalabrutinib
Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions.
Intervention: CT scans
Rituximab and Acalabrutinib
Participants will receive treatment of Rituximab weekly for 4 weeks, and Acalabrutinib twice daily for 4 weeks. Response assessment via diagnostic CT scans will dictate further treatment decisions.
Intervention: Acalabrutinib
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: Up to 8 weeks after treatment
ORR will be estimated along with 90% Confidence Intervals (CIs), and compared against the null using exact binomial test. Logistic regression model will be used to identify factors associated with response status.
Secondary Outcomes
- Duration of Response (DOR)(Up to 3 years after treatment)
- Progression Free Survival (PFS)(at 24 months after treatment)
- Overall Survival (OS)(Up to 3 years after treatment)
- Time to Treatment Failure (TTF)(Up to 3 years after treatment)
- Number of Participants With a Grade 3 Adverse Event (AE) or Higher(Up to 3 years after treatment)
- Complete Response Rate (CRR)(at 24 months after treatment)
- Partial Response Rate (PRR)(at 24 months after treatment)