Clinical Trials /

Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

NCT04094142

Description:

NCCN guidelines for B cell lymphoma suggest that patients with relapsed/refractory aggressive NHL who are candidate for high-dose therapy should receive combination of cytotoxic chemotherapies as 2nd line treatment. However, proportion of patients who are adequately salvaged by second line chemotherapy and high-dose chemotherapy with stem cell rescue is unsatisfactory. Moreover, many fragile patients are unfit for salvage cytotoxic chemotherapy and/or high-dose chemotherapy. Hence, most of patients with relapsed/refractory aggressive B-cell NHL is ultimately candidate for less-cytotoxic drugs with targeted approach. This trial is phase II trial of acalabrutinib in combination with rituximab and lenalidomide for these patients.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Richter Syndrome
  • Small Lymphocytic Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
  • Official Title: Phase II Trial of Acalabrutinib With Rituximab and Lenalidomide in Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 1811-092-988
  • NCT ID: NCT04094142

Conditions

  • Non-hodgkin Lymphoma,B Cell

Interventions

DrugSynonymsArms
AcalabrutinibLenalidomide, RituximabTreatment arm

Purpose

NCCN guidelines for B cell lymphoma suggest that patients with relapsed/refractory aggressive NHL who are candidate for high-dose therapy should receive combination of cytotoxic chemotherapies as 2nd line treatment. However, proportion of patients who are adequately salvaged by second line chemotherapy and high-dose chemotherapy with stem cell rescue is unsatisfactory. Moreover, many fragile patients are unfit for salvage cytotoxic chemotherapy and/or high-dose chemotherapy. Hence, most of patients with relapsed/refractory aggressive B-cell NHL is ultimately candidate for less-cytotoxic drugs with targeted approach. This trial is phase II trial of acalabrutinib in combination with rituximab and lenalidomide for these patients.

Trial Arms

NameTypeDescriptionInterventions
Treatment armExperimentalAcalabrutinib is provided as hard gelatin capsules for oral administration. Acalabrutinib 100 mg will be administered approximately every 12 hours from day 1 to day 28 Rituximab is provided as single-use vials for intravenous administration only. Rituximab 375 mg/m2 will be administered on day 1. Lenalidomide is provided as opaque hard capsules for oral administration. Lenalidomide 20 mg will be administered once daily from day 1 to day 21
  • Acalabrutinib

Eligibility Criteria

        Inclusion Criteria:

          1. Men and women ≥ 18 years of age.

          2. Diagnosed with aggressive B cell non-Hodgkin lymphoma

               -  Diffuse large B cell lymphoma (Both GCB and non-GCB)

                  : GCB type should not be more than 40% (N=26) of whole study population (Would
                  limit number of GCB patients by maximum of 26)

               -  Primary mediastinal B cell lymphoma

               -  Transformed follicular lymphoma

               -  Small lymphocytic lymphoma with Richter transformation

          3. Failed previous treatments and last dose administered must be more than 2-week ahead
             from enrollment

               -  Should have received anti-CD20 based chemotherapy previously

               -  Failed at least two lines of therapy if patient is candidate for autologous stem
                  cell transplantation

               -  Failed frontline therapy if patient is ineligible for autologous stem cell
                  transplantation

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          5. Woman of childbearing potential (WOCBP) who are sexually active must have 2 negative
             urine hCG test prior to first dose, then every week for the first month of study
             period, then every 4 weeks afterwards during treatment period if menses are regular or
             every 2 weeks if menses are irregular. Urine hCG test must be done 4 weeks after the
             last dose of acalabrutinib, lenalidomide and rituximab. WOCBP must use 2 methods
             including at least 1 highly effective method of contraception for 4 weeks prior to
             first dose, during treatment period and for 4 weeks after the last dose of
             acalabrutinib, lenalidomide and for 12 months after the last dose of rituximab. Men
             who are sexually active must use condoms during treatment period and 4 weeks after the
             last dose of any study drug.

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

          7. Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information.

        Exclusion Criteria:

          1. Diagnosed with mantle cell lymphoma

          2. Previously treated with more than four lines of chemotherapy (Consolidative autologous
             stem cell transplantation is deemed as the same line therapy)

          3. Previously treated with allogeneic hematopoietic stem cell transplantation within 6
             months

          4. GVHD requiring treatment

          5. Patient who cannot take drug per oral

          6. Known resistance to both BTK inhibitor and lenalidomide (Progression free survival to
             both BTK inhibitor and lenalidomide < 6 months)

          7. Known resistant mutation to BTK inhibitor (BTKC481S and PLGCR665W)

          8. 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,
             or other cancer from which the subject has been disease free for ≥ 5 years or which
             will not limit survival to < 5 years.

          9. 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 on study.

         10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel that is likely to affect absorption,
             symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or
             gastric restrictions and bariatric surgery, such as gastric bypass.

         11. Known history of infection with HIV or any uncontrolled active systemic infection (eg,
             bacterial, viral or fungal).

         12. Known history of drug-specific hypersensitivity or anaphylaxis to study drug
             (including active product or excipient components).

         13. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand
             disease).

         14. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic
             purpura).

         15. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.

         16. Requires or receiving anticoagulation with warfarin or equivalent vitamin K
             antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.

         17. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.

         18. 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.

         19. History of significant cerebrovascular disease or event, including stroke or
             intracranial hemorrhage, within 6 months before the first dose of study drug.

         20. Major surgical procedure within 28 days of first dose of study drug. Note: 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.

         21. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody
             (anti-HBc) positive and who are surface antigen negative will need to have a negative
             polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg)
             positive or hepatitis B PCR positive will be excluded. Those who are positive only for
             anti-HBc and negative for HbsAg and hepatitis B PCR need to receive adequate antiviral
             prophylaxis for hepatitis B during the study period.

             Subjects who are hepatitis C antibody positive will need to have a negative PCR
             result. Those who are hepatitis C PCR positive will be excluded.

         22. Active tuberculosis (history of exposure or history of positive tuberculin test; plus
             presence of clinical symptoms, physical or radiographic findings). Subjects with
             latent tuberculosis infection who are deemed to require treatment by the investigator
             are not eligible.

         23. Uncontrolled active infection as determined by the investigator.

         24. WBC < 3,000 /μL, ANC < 1,000 /μL, Platelets < 75,000 /μL, or Hemoglobin < 9.0 g/dL.
             Correction with transfusion within 2 weeks is not allowed.

         25. Total bilirubin > 2 x ULN, or AST, ALT > 3 x ULN

         26. Cr > 1.5 x ULN or CLcr < 30 mL/min/1.73m2

         27. Breastfeeding or pregnant.

         28. Concurrent participation in another therapeutic clinical trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:within 4 weeks after the 6 cycles of combination therapy (each cycle is 28 days)
Safety Issue:
Description:ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Lugano criteria

Secondary Outcome Measures

Measure:Duration of response
Time Frame:Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)
Safety Issue:
Description:
Measure:Complete remission rate
Time Frame:Response will be assessed at Week 8, 16, 24 (± 7 days)
Safety Issue:
Description:
Measure:Progression free survival
Time Frame:Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)
Safety Issue:
Description:
Measure:Overall survival
Time Frame:Tumor status will be assessed at Week 8, 16, 24 (± 7 days), then every 3 months (± 14 days)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seoul National University Hospital

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