Clinical Trials /

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

NCT04189952

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Transformed Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Acalabrutinib in Combination With R-ICE For Relapsed or Refractory Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 20190706
  • NCT ID: NCT04189952

Conditions

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

Interventions

DrugSynonymsArms
AcalabrutinibACP-196Acalabrutinib + R-ICE
RituximabRituxanAcalabrutinib + R-ICE
IfosfamideIfex, IsophosphamideAcalabrutinib + R-ICE
CarboplatinParaplatinAcalabrutinib + R-ICE
EtoposideEtopophos, Toposar, VePesidAcalabrutinib + R-ICE

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Acalabrutinib + R-ICEExperimentalAcalabrutinib 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.
  • Acalabrutinib
  • Rituximab
  • Ifosfamide
  • Carboplatin
  • Etoposide

Eligibility Criteria

        Inclusion Criteria:

          1. Men and women ≥ 18 years of age.

          2. Patients must have histologic confirmation of relapsed or refractory lymphoma.

          3. 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.

          4. Patient must have been previously treated for B cell non-Hodgkin lymphoma with any of
             the allowable below:

               1. First-line treatment with rituximab and an anthracycline-based chemotherapy.

               2. Monotherapy rituximab, dosed prior to first-line rituximab combined with
                  anthracycline containing chemotherapy, or as maintenance therapy.

               3. Radiotherapy as part of the first-line treatment plan including anthracycline and
                  rituximab.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

          6. Life expectancy of greater than 6 weeks.

          7. Patients must have normal organ and marrow function as defined below,

               1. absolute neutrophil count ≥ 1000/microliters (mcL) (unless due to lymphoma
                  involvement of the bone marrow),

               2. platelets ≥75,000/mcL (unless due to lymphoma involvement of the bone marrow),

               3. total bilirubin <1.5 x within normal institutional limits (unless due to lymphoma
                  involvement of liver or a known history of Gilbert's disease),

               4. Aspartate transaminase (AST) (SGOT)/Alanine transaminase (ALT) (SGPT) ≤ 2.5 ×
                  institutional upper limit of normal (unless due to lymphoma involvement of
                  liver),

               5. creatinine within normal institutional limits, or

               6. creatinine clearance ≥40 mL/min/1.73 m2 for patients with creatinine levels above
                  institutional normal. (unless due to lymphoma).

          8. 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.

          9. 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.

         10. 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.

         11. Men must agree to refrain from sperm donation during the study and for 90 days after
             the last dose of study drug.

         12. Willing and able to participate in all required evaluations and procedures in this
             study protocol including swallowing capsules without difficulty.

         13. 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).

        Exclusion Criteria:

          1. Germinal-center cell-of-origin DLBCL.

          2. 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.

          3. Patients who are receiving any other investigational agents.

          4. Patients with known central nervous system involvement of lymphoma.

          5. 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.

          6. 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.

          7. 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.

          8. 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.

          9. Patients may not have received any anti-cancer therapy for their primary rel/ref DLBCL
             with the exception of palliative radiation therapy (RT).

         10. 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.

         11. Presence of transfusion-dependent thrombocytopenia.

         12. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor.

         13. History of prior malignancy, with the exception of the following:

               1. Malignancy treated with curative intent felt to be at low risk for recurrence by
                  treating physician,

               2. Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma
                  without current evidence of disease,

               3. Adequately treated cervical carcinoma in situ without current evidence of
                  disease.

         14. 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.

         15. 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.

         16. 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.

         17. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

         18. 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.

         19. Received anticoagulation therapy with Coumadin or equivalent vitamin K antagonists
             within the last 28 days.

         20. Vaccinated with live, attenuated vaccines with 4 weeks of first does of study drug.

         21. 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.

         22. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.

         23. Unwilling or unable to participate in all required study evaluations and procedures.

         24. Currently active, clinically significant hepatic impairment (≥ moderate hepatic
             impairment according to the NCI/Child Pugh classification.

         25. Breastfeeding or pregnant.

         26. Concurrent participation in another therapeutic clinical trial.

         27. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Complete Response (CR)
Time Frame:9 weeks (End of Cycle 3)
Safety Issue:
Description:Rate of complete response (CR) in study participants will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.

Secondary Outcome Measures

Measure:Incidence of Toxicity
Time Frame:13 weeks
Safety Issue:
Description:The safety profile and tolerability of acalabrutinib + R-ICE will be reported as the number of incidents 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.
Measure:Rate of Partial Response (PR)
Time Frame:9 weeks
Safety Issue:
Description:Rate of partial response (PR) in study participants will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria.
Measure:Overall Rate of Response (ORR)
Time Frame:9 weeks
Safety Issue:
Description:ORR is defined as the proportion 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.
Measure:Mobilization Rate of CD34+ cells
Time Frame:9 weeks
Safety Issue:
Description:Proportion 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.
Measure:Event-Free Survival (EFS)
Time Frame:Up to 1 Year After End of Therapy
Safety Issue:
Description:Median 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.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 1 Year After End of Therapy
Safety Issue:
Description:Median 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).
Measure:Overall Survival (OS)
Time Frame:Up to 1 Year After End of Therapy
Safety Issue:
Description:Median 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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Miami

Trial Keywords

  • Non-Germinal Center Diffuse Large B Cell Lymphoma

Last Updated

December 4, 2019