Diffuse Large B Cell LymphomaPhase 2NCT04189952
Acalabrutinib in Combination With R-ICE For Relapsed or Refractory Lymphoma
A Phase 2 study testing Acalabrutinib, Rituximab and Ifosfamide in people with Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia, run by University of Miami at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
- What is being tested?
- Acalabrutinib, Rituximab and Ifosfamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2020to 1 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
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- 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),
- total bilirubin <1.5 x within normal institutional limits (unless due to lymphoma involvement of liver or a known history of Gilbert's disease),
- Aspartate transaminase (AST) (SGOT)/Alanine transaminase (ALT) (SGPT) ≤ 2.5 × institutional upper limit of normal (unless due to lymphoma involvement of liver),
- creatinine within normal institutional limits, or
- creatinine clearance ≥40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. (unless due to lymphoma).
- Major surgical procedure within 28 days of first dose of study drug. If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- Women who are sexually active and can bear children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib + R-ICE.
- Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of acalabrutinib + R-ICE.
- Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of study drug.
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules 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 subject privacy regulations).
Who cannot join
- 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.
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- 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,
- Adequately treated cervical carcinoma in situ without current evidence of disease.
- Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to first dose with study drug.
- Unable to swallow capsules, or disease significantly affecting gastrointestinal function or, resection of the stomach or small bowel, or symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody will need a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.) Hepatitis C antibody positive patients are eligible if PCR is negative. Hepatitis B core antibody (+) patients without evidence of HBsAg or Hep B PCR (+) are eligible with appropriate Hepatitis B reactivation prophylaxis.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study at risk.
- Received anticoagulation therapy with Coumadin or equivalent vitamin K antagonists within the last 28 days.
- Vaccinated with live, attenuated vaccines with 4 weeks of first does of study drug.
- Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 5), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
- Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- Unwilling or unable to participate in all required study evaluations and procedures.
- Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the NCI/Child Pugh classification.
- Breastfeeding or pregnant.
- Concurrent participation in another therapeutic clinical trial.
- Patients who require proton pump inhibitors at baseline (prior to fist dose of study drug) or strong CYP3A4 inhibitor or inducer and are not able to switch to another medication
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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
- Being tested
- Acalabrutinib, Rituximab, Ifosfamide, Carboplatin, Etoposide
- Keywords
- Non-Germinal Center Diffuse Large B Cell Lymphoma
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called ACP-196
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.
RituximabDrug
Also called Rituxan
Rituximab 375 mg/m2 administered intravenously (IV) on Day 1 of each cycle.
IfosfamideDrug
Also called Ifex, Isophosphamide
Ifosfamide 5g/m2 administered intravenously (IV) over 24 hours on Day 2 of each cycle.
CarboplatinDrug
Also called Paraplatin
Carboplatin Area Under the Concentration time Curve (AUC) 5 IV administered intravenously (IV) on Day 2 of each cycle.
EtoposideDrug
Also called Etopophos, Toposar, VePesid
Etoposide 100 mg/m2 administered intravenously (IV) on Days 1, 2 and 3 of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Acalabrutinib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9 weeks (End of Cycle 3)
Secondary outcomes (7)
Number of Treatment-Emergent Adverse Events
The safety profile and tolerability of acalabrutinib + R-ICE will be reported as the number of treatment-emergent adverse events (AEs) or abnormalities of laboratory tests; serious adverse events (SAEs); dose-limiting toxicities (DLTs), or AEs leading to discontinuation of study treatment, or death. Severity and relationship will be assessed by the treating physician using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.
Measured: 13 weeks
Percentage of Participants Achieving Partial Response (PR)
The percentage of participants achieving partial response (PR) will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.
Measured: 9 weeks
Percentage of Participants Achieving Overall Response
Overall response is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) to acalabrutinib + R-ICE therapy. Response will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.
Measured: 9 weeks
Percentage of Participants Achieving Mobilization Rate Greater Than or Equal to 2x10^6 CD34+ Cells/kg Body Weight
Percentage of study participants achieving a mobilization rate of greater than or equal to 2x10^6 CD34+ cells/kg body weight. Descriptive statistics will be used to summarize the mobilization rates.
Measured: 9 weeks
Event-Free Survival (EFS)
Duration of Event-Free Survival (EFS) in study participants. EFS is defined as the time from first dose to documented disease progression, death from any cause, or study dropout, whichever occurs first.
Measured: Up to 61 weeks
Progression-Free Survival (PFS)
Duration of Progression-Free Survival (PFS) in study participants. PFS is defined as the time from first dose to documented disease progression, or death from any cause, whichever occurs first. Data for subjects who are still alive and free from progression at the time of data cutoff date, lost to follow-up, or have discontinued the study will be censored on last assessment (or, if no post-baseline tumor assessment, at the time of first dose plus 1 day).
Measured: Up to 61 weeks
Overall Survival (OS)
Duration of Overall Survival (OS) in study participants. OS is defined as the time from first dose to death from any cause. Data for subjects who are still alive at the time of data cutoff date, lost to follow-up, have discontinued the study (or, if no post-baseline assessment, at the time of first dose plus 1 day) will be censored.
Measured: Up to 61 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2019
- Study start22 Sep 2020
- Primary completion30 Jun 2021
- Study completion1 Mar 2022
Why it stopped: Investigator Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Craig Moskowitz, University of Miami
- Investigators
- Craig Moskowitz, MD, Principal investigator, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04189952
- Sponsor's protocol ID
- 20190706
- Status last verified
- May 2025
- First submitted
- 4 Dec 2019
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04189952
- Acronym / sponsor ID
- 20190706
- Conditions
- Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, Marginal Zone Lymphoma
- Keywords
- Non-Germinal Center Diffuse Large B Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigator Decision
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 22 Sep 2020 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 6 Dec 2019 (actual)
- Results
- Posted 19 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acalabrutinib + R-ICE | Experimental | Drug: Acalabrutinib, Drug: Rituximab, Drug: Ifosfamide, Drug: Carboplatin, Drug: EtoposideAcalabrutinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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.
- Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of the allowable below:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
Key exclusion criteria (30 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: ACP-196Acalabrutinib 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. | Drug | Acalabrutinib + R-ICE |
| RituximabAlso: RituxanRituximab 375 mg/m2 administered intravenously (IV) on Day 1 of each cycle. | Drug | Acalabrutinib + R-ICE |
| IfosfamideAlso: Ifex, IsophosphamideIfosfamide 5g/m2 administered intravenously (IV) over 24 hours on Day 2 of each cycle. | Drug | Acalabrutinib + R-ICE |
| CarboplatinAlso: ParaplatinCarboplatin Area Under the Concentration time Curve (AUC) 5 IV administered intravenously (IV) on Day 2 of each cycle. | Drug | Acalabrutinib + R-ICE |
| EtoposideAlso: Etopophos, Toposar, VePesidEtoposide 100 mg/m2 administered intravenously (IV) on Days 1, 2 and 3 of each cycle. | Drug | Acalabrutinib + R-ICE |
Primary outcome
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.
7 secondary outcomes
Number of Treatment-Emergent Adverse Events
Time frame: 13 weeks
Percentage of Participants Achieving Partial Response (PR)
Time frame: 9 weeks
Percentage of Participants Achieving Overall Response
Time frame: 9 weeks
Percentage of Participants Achieving Mobilization Rate Greater Than or Equal to 2x10^6 CD34+ Cells/kg Body Weight
Time frame: 9 weeks
Event-Free Survival (EFS)
Time frame: Up to 61 weeks
Progression-Free Survival (PFS)
Time frame: Up to 61 weeks
Overall Survival (OS)
Time frame: Up to 61 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Moskowitz, MD principal investigator
University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acalabrutinib, Rituximab and Ifosfamide in people with Diffuse Large B Cell Lymphoma and Chronic Lymphocytic Leukemia, run by University of Miami at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Complete Response (CR) (time frame: 9 weeks (End of Cycle 3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.