Acalabrutinib in Combination With R-ICE For Relapsed or Refractory Lymphoma

NCT04189952 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20190706
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B Cell Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Leukemia; Marginal Zone Lymphoma

Keywords

Non-Germinal Center Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Complete Response (CR)

  The percentage of participants achieving complete response (CR) will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.

  9 weeks (End of Cycle 3)

Secondary Outcomes (7)

• Number of Treatment-Emergent Adverse Events

  13 weeks

• Percentage of Participants Achieving Partial Response (PR)

  9 weeks

• 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

• Event-Free Survival (EFS)

  Up to 61 weeks

Study Arms (1)

Acalabrutinib + R-ICE

EXPERIMENTAL

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.

Drug: Acalabrutinib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

Interventions

Acalabrutinib DRUG

Acalabrutinib 100 mg capsules taken by mouth every 12 hours (PO BID), for a total of 2 daily doses on Days 1 to 21 of each cycle.

Also known as: ACP-196

Acalabrutinib + R-ICE

Rituximab DRUG

Rituximab 375 mg/m2 administered intravenously (IV) on Day 1 of each cycle.

Also known as: Rituxan

Acalabrutinib + R-ICE

Ifosfamide DRUG

Ifosfamide 5g/m2 administered intravenously (IV) over 24 hours on Day 2 of each cycle.

Also known as: Ifex, Isophosphamide

Acalabrutinib + R-ICE

Carboplatin DRUG

Carboplatin Area Under the Concentration time Curve (AUC) 5 IV administered intravenously (IV) on Day 2 of each cycle.

Also known as: Paraplatin

Acalabrutinib + R-ICE

Etoposide DRUG

Etoposide 100 mg/m2 administered intravenously (IV) on Days 1, 2 and 3 of each cycle.

Also known as: Etopophos, Toposar, VePesid

Acalabrutinib + R-ICE

Eligibility Criteria

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

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Life expectancy of greater than 6 weeks.
• Patients must have normal organ and marrow function as defined below,
• absolute neutrophil count ≥ 1000/microliters (mcL) (unless due to lymphoma involvement of the bone marrow),
• platelets ≥75,000/mcL (unless due to lymphoma involvement of the bone marrow),

You may not qualify if:

• 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.
• Presence of transfusion-dependent thrombocytopenia.
• Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.
• History of prior malignancy, with the exception of the following:
• Malignancy treated with curative intent felt to be at low risk for recurrence by treating physician,
• Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease,

Sponsors & Collaborators

• University of Miami: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone

Interventions

acalabrutinib; Rituximab; Ifosfamide; Carboplatin; Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Limitations and Caveats

To protect participant privacy and maintain confidentiality, results will not be reported.

Results Point of Contact

• Title: Craig Moskowitz, MD
• Organization: University of Miami

chm78@med.miami.edu

305-243-9009

Study Officials

• Craig Moskowitz, MD

  University of Miami

  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: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 6, 2019
• Study Start: September 22, 2020
• Primary Completion: June 30, 2021
• Study Completion: March 1, 2022
• Last Updated: May 31, 2025
• Results First Posted: September 19, 2022

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)