A Phase 2, Open-Label Study of Acalabrutinib in Combination With R-ICE For Relapsed or Refractory Non-Germinal Center Diffuse Large B Cell Lymphoma, Transformed Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia or Transformed Marginal Zone Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Acalabrutinib
- Conditions
- Diffuse Large B Cell Lymphoma
- Sponsor
- University of Miami
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Percentage of Participants Achieving Complete Response (CR)
- Status
- Terminated
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study is to test a combination treatment of acalabrutunib when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) to evaluate if it will be able to improve durable responses and cure some patients.
Investigators
Craig Moskowitz
Professor
University of Miami
Eligibility Criteria
Inclusion Criteria
- •Men and women ≥ 18 years of age.
- •Patients must have histologic confirmation of relapsed or refractory lymphoma.
- •Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
- •a) CT scan showing at least:
- •i. 2 or more clearly demarcated lesions/nodes with a long axis \>1.5cm and short axis ≥ 1.0cm, or
- •ii. 1 clearly demarcated lesion/node with a long axis \>2.0cm and short axis ≥1.0cm.
- •Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of the allowable below:
- •First-line treatment with rituximab and an anthracycline-based chemotherapy.
- •Monotherapy rituximab, dosed prior to first-line rituximab combined with anthracycline containing chemotherapy, or as maintenance therapy.
- •Radiotherapy as part of the first-line treatment plan including anthracycline and rituximab.
Exclusion Criteria
- •Germinal-center cell-of-origin DLBCL.
- •Patients who have had chemotherapy or radiotherapy \< 21 days prior to first administration of study treatment or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patients who are receiving any other investigational agents.
- •Patients with known central nervous system involvement of lymphoma.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to acalabrutinib or R-ICE with the exception of first-infusion reaction to rituximab.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Recent infections requiring systemic treatment need to have completed therapy \> 7 days before the first dose of study drug.
- •Pregnant women are excluded from this study because an acalabrutinib R-ICE is a chemotherapy program with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with acalabrutinib R-ICE, breastfeeding should be discontinued if the mother is treated with acalabrutinib R-ICE.
- •HIV-positive patients on combination antiretroviral therapy are eligible, unless the patient's CD4 count is below the institutional lower limit of normal, or the patient is taking prohibited CYP3A4/5 strong inhibitors or inducers.
- •Patients may not have received any anti-cancer therapy for their primary rel/ref DLBCL with the exception of palliative radiation therapy (RT).
- •Uncontrolled Autoimmune Hemolytic Anemia or immune thrombocytopenia purpura (ITP) resulting in (or as evidenced by) declining platelet or Hgb levels within the 4 weeks prior to first dose of study drug.
Arms & Interventions
Acalabrutinib + R-ICE
Acalabrutinib in combination with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). All participants will receive combination treatment for 3 cycles. Each cycle lasts 21 consecutive days. Combination treatment includes twice daily dose of Acalabrutinib, Rituximab on Day 1 of each cycle, Ifosfamide and Carboplatin on Day 2 of each cycle, and Etoposide on Days 1-3 of each cycle.
Intervention: Acalabrutinib
Acalabrutinib + R-ICE
Acalabrutinib in combination with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). All participants will receive combination treatment for 3 cycles. Each cycle lasts 21 consecutive days. Combination treatment includes twice daily dose of Acalabrutinib, Rituximab on Day 1 of each cycle, Ifosfamide and Carboplatin on Day 2 of each cycle, and Etoposide on Days 1-3 of each cycle.
Intervention: Rituximab
Acalabrutinib + R-ICE
Acalabrutinib in combination with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). All participants will receive combination treatment for 3 cycles. Each cycle lasts 21 consecutive days. Combination treatment includes twice daily dose of Acalabrutinib, Rituximab on Day 1 of each cycle, Ifosfamide and Carboplatin on Day 2 of each cycle, and Etoposide on Days 1-3 of each cycle.
Intervention: Ifosfamide
Acalabrutinib + R-ICE
Acalabrutinib in combination with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). All participants will receive combination treatment for 3 cycles. Each cycle lasts 21 consecutive days. Combination treatment includes twice daily dose of Acalabrutinib, Rituximab on Day 1 of each cycle, Ifosfamide and Carboplatin on Day 2 of each cycle, and Etoposide on Days 1-3 of each cycle.
Intervention: Carboplatin
Acalabrutinib + R-ICE
Acalabrutinib in combination with rituximab, ifosfamide, carboplatin and etoposide (R-ICE). All participants will receive combination treatment for 3 cycles. Each cycle lasts 21 consecutive days. Combination treatment includes twice daily dose of Acalabrutinib, Rituximab on Day 1 of each cycle, Ifosfamide and Carboplatin on Day 2 of each cycle, and Etoposide on Days 1-3 of each cycle.
Intervention: Etoposide
Outcomes
Primary Outcomes
Percentage of Participants Achieving Complete Response (CR)
Time Frame: 9 weeks (End of Cycle 3)
The percentage of participants achieving complete response (CR) will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.
Secondary Outcomes
- Percentage of Participants Achieving Overall Response(9 weeks)
- Percentage of Participants Achieving Mobilization Rate Greater Than or Equal to 2x10^6 CD34+ Cells/kg Body Weight(9 weeks)
- Number of Treatment-Emergent Adverse Events(13 weeks)
- Percentage of Participants Achieving Partial Response (PR)(9 weeks)
- Event-Free Survival (EFS)(Up to 61 weeks)
- Progression-Free Survival (PFS)(Up to 61 weeks)
- Overall Survival (OS)(Up to 61 weeks)