Rituximab and Acalabrutinib in Newly Diagnosed B Cell Post Transplant Lymphoproliferative Disorder

NCT04337827 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE3419
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-transplant Lymphoproliferative Disorder

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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.

  Up to 8 weeks after treatment

Secondary Outcomes (13)

• Complete Response Rate (CRR)

  at 6 months after treatment

• Complete Response Rate (CRR)

  at 12 months after treatment

• Complete Response Rate (CRR)

  at 24 months after treatment

• Partial Response Rate (PRR)

  at 6 months after treatment

• Partial Response Rate (PRR)

  at 12 months after treatment

Study Arms (1)

Rituximab and Acalabrutinib

EXPERIMENTAL

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.

Drug: Rituximab; Drug: Acalabrutinib; Diagnostic Test: CT scans

Interventions

Rituximab DRUG

Weekly x 4 weeks. If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto Long Term Follow Up (LTFU).

Also known as: Rituxan, Mabthera

Rituximab and Acalabrutinib

Acalabrutinib DRUG

100mg twice per day (BID) x 4 weeks (28 day cycle) If diagnostic test reveals complete response, then participant will continue with one additional 28 day cycle. If partial response, then proceed with 3 additional 28 day cycles. If stable disease or progression of disease, then go off study treatment and proceed onto LTFU.

Also known as: ACP-196

Rituximab and Acalabrutinib

CT scans DIAGNOSTIC_TEST

2 weeks (day 36 ± 5 days) after end of cycle 1 treatment.

Rituximab and Acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a biopsy confirmed newly diagnosed CD20 positive B cell PTLD.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 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)
• Alanine aminotransferase/aspartate aminotransferase (ALT/AST) \< 2.5 X or ≤5X ULN for patients with document hepatic involvement with lymphoma
• Women of childbearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) during treatment and for 12 months after last dose of study treatment. Women who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Subjects must be willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
• Subjects must have the ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

You may not qualify if:

• 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).
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon)
• Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
• History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.

Sponsors & Collaborators

• Deepa Jagadeesh: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

Rituximab; acalabrutinib; Tomography, X-Ray Computed

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography

Limitations and Caveats

Early termination leading to small numbers of subjects, unable to perform analysis of data.

Results Point of Contact

• Title: Dr. Deepa Jagadeesh
• Organization: Cleveland Clinic Foundation, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

1-866-223-8100

Study Officials

• Deepa Jagadeesh, MD, MPH

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 8, 2020
• Study Start: September 2, 2020
• Primary Completion: June 27, 2022
• Study Completion: December 19, 2022
• Last Updated: April 10, 2024
• Results First Posted: April 10, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)