Clinical Trials /

Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma

NCT04402138

Description:

This is a phase II study to evaluate efficacy of Acalabrutinib as a maintenance therapy following blood or marrow transplant (BMT) in patients who have been diagnosed with mantle cell lymphoma.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treatment With Acalabrutinib Post Blood or Marrow Transplantation in Subjects With Mantle Cell Lymphoma
  • Official Title: Single Arm, Phase II Study of Acalabrutinib as Post-Autologous Blood or Marrow Transplant (BMT) Maintenance Therapy in Subjects With Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: LYM 155
  • NCT ID: NCT04402138

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
AcalabrutinibCalquenceAcalabrutinib

Purpose

This is a phase II study to evaluate efficacy of Acalabrutinib as a maintenance therapy following blood or marrow transplant (BMT) in patients who have been diagnosed with mantle cell lymphoma.

Detailed Description

      Mantle cell lymphoma (MCL) is one of approximately 100 different types of non-Hodgkin's
      lymphoma (NHL). Due to the aggressive and heterogeneous nature of MCL, majority of patients
      are diagnosed with advanced stage disease that requires immediate, diverse and aggressive
      courses of therapy to improve the outcome of the disease. The addition of blood or bone
      marrow transplantation (BMT) to the chemotherapy regimens is a critical factor to prolong
      duration of response in patients, however, the benefit of combination chemotherapy followed
      by BMT is often temporary as patients experience disease progression and mortality and this
      underscores the need for novel therapies as well as additional maintenance therapy strategies
      to prevent relapse post-BMT.

      Acalabrutinib, a selective, irreversible small molecule inhibitor of Bruton's tyrosine kinase
      (BTK) is approved for the treatment of adult patients with MCL who have received at least 1
      prior therapy

      This study is a single arm, multi-center, phase 2 study of subjects who will receive
      acalabrutinib as maintenance therapy post-BMT. Subjects will undergo a standard of care BMT
      with conditioning regimen determined by the treating physician per institutional
      guidelines.The BMT is not considered part of this study. Following completion of the BMT,
      Maintenance therapy with acalabrutinib will begin on Day 100 in 28-day cycles. Subjects will
      self-administer 100 mg acalabrutinib BID until they reach 2 years post-BMT (approximately 22
      cycles).Subjects will be followed for up to 5 years post-BMT for Progression Free Survival.
    

Trial Arms

NameTypeDescriptionInterventions
AcalabrutinibExperimentalAcalabrutinib will be self-administered orally for up to approximately 2 years post-BMT.
  • Acalabrutinib

Eligibility Criteria

        Inclusion Criteria:

        Inclusion Criteria for Initial Enrollment (Screening #1):

        Patients must meet all of the following criteria in order to be included in this research
        study:

          1. Written informed consent, according to local guidelines, signed by the subject or by a
             legal guardian prior to the performance of any study-related screening procedures.

          2. Men and women ≥18 years-of-age at the time of signature of the informed consent form
             (ICF).

          3. A diagnosis of MCL confirmed by one of the following:

               -  t(11;14) detected by fluorescence in situ hybridization (FISH), conventional
                  cytogenetics, or other molecular evaluation

               -  expression of cyclin D1 confirmed by immunohistochemistry.

          4. Subject must have completed induction chemotherapy and plan to and be eligible to
             receive their first BMT per standard of care.

          5. Availability of an archival paraffin-embedded tumor block for MRD testing.

          6. The Investigator anticipates that the subject will meet the appropriate lab
             requirements listed in Screening #2 by Day 100.

          7. Patients who received prior therapy with a BTK inhibitor are eligible to enroll.

        Inclusion Criteria Post-BMT, Prior to Day 100 (Screening #2):

          1. Adequate organ system function defined as:

               -  Absolute neutrophil count (ANC) ≥1,000/mm3.

               -  Total bilirubin ≤1.5 x the upper limit of normal (ULN) (except for previously
                  documented Gilbert's syndrome)

               -  Platelet count ≥75,000/mm3. Platelet infusions to meet eligibility criteria are
                  not allowed within 3 days of study enrollment.

               -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN

               -  Calculated creatinine clearance (CrCl) ≥30 mL/min as calculated by the
                  CockcroftGault method. Estimated CrCl (glomerular filtration rate [GFR]) =
                  (140-age [years]) x (weight [kg]) x Fa /(72 x serum creatinine [mg/dL]) a where F
                  = 0.85 for females and F = 1 for males

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

          3. Subjects who did not receive an anti-cancer therapy (including surgery, radiotherapy,
             chemotherapy, immunotherapy, or investigational therapy) during the time between their
             transplant and the start of study therapy. Subjects must have recovered (e.g., Grade
             ≤1 or baseline) from AEs associated with prior cancer therapy. Note: Subjects with
             Grade ≤2 neuropathy or Grade ≤2 alopecia are an exception to the latter criterion and
             may qualify for the study.

          4. Woman of childbearing potential (WoCBP) who are sexually active with male partners
             must use highly effective methods of contraception during treatment and for 2 days
             after the last dose of acalabrutinib. For male subjects with a pregnant or
             non-pregnant WoCBP partner, no contraception measures are required. A WoCBP must have
             a negative pregnancy test (urine or serum) at the time of screening and 72 hours
             before starting the study drug or have evidence of non-childbearing potential by
             fulfilling one of the following criteria:

               -  Post-menopausal women, defined as either women aged >50 years and amenorrheic for
                  ≥12 months following cessation of all exogenous hormonal treatments or women <50
                  years old who have been amenorrheic for ≥12 months following the cessation of
                  exogenous hormonal treatments, and have serum follicle- stimulating hormone (FSH)
                  and luteinizing hormone (LH) levels in the post- menopausal range for the
                  institution.

               -  Documentation of irreversible surgical sterilization by hysterectomy, bilateral
                  oophorectomy or bilateral salpingectomy, but not tubal ligation

               -  Medically confirmed, irreversible premature ovarian failure.

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

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

        Exclusion Criteria:

        Patients who meet any of the following criteria will be excluded from study entry:

          1. Subjects who have relapsed or progressed at any time prior to BM

          2. Subjects with known mutations that confer resistance to a BTK inhibitor.

          3. Confirmed clinical PD since the time of BMT

          4. Prior malignancy (or any other malignancy requiring 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 ≥2 years or that will
             not limit survival to <2 years. The exceptions are:

               -  Subjects treated with curative intent >2 years prior to enrollment and have a low
                  probability of recurrence.

          5. 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.

          6. Malabsorption syndrome, disease significantly affecting gastrointestinal function,
             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.

          7. Known history of infection with human immunodeficiency virus (HIV) or any uncontrolled
             active systemic bacterial, fungal, parasitic or viral infection. Infections are
             considered controlled if appropriate therapy has been instituted and, at the time of
             screening, no signs of infection progression are present.

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

          9. Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand
             disease).

         10. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.

         11. Requires treatment with a strong CYP3A4 inhibitor/inducer

         12. Requires or is receiving anticoagulation treatment with warfarin or equivalent vitamin
             K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.

         13. Prothrombin time (PT)/ international normalized ratio (INR) or activated partial
             thromboplastin time (aPTT) >2 x ULN (in the absence of lupus anticoagulant).

         14. Requires treatment with proton-pump inhibitors (e.g., 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.

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

         16. 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.

         17. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody
             (anti-HBc) positive and who are hepatitis B surface antigen (HbsAg) negative will need
             to have a negative PCR result. Those who are HbsAg positive or hepatitis B PCR
             positive will be excluded. 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.

         18. Breastfeeding or pregnant.

         19. Concurrent participation in another therapeutic clinical trial.

         20. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol and/or follow-up procedures outlined in the protocol.

         21. The inability to swallow capsules.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival Rate (PFS)
Time Frame:Assessed with CT/MRI/FGD-PET scans for up to 24 months
Safety Issue:
Description:Progression Free Survival Rate is defined as the number of subjects who are alive and free of disease progression or relapse according to RECIL for up to 2 years post-BMT. According to RECIL, disease progression is defined as following criteria: >20% increase in sum of longest diameters of target lesions. For small lymph nodes measuring <15 mm post therapy, a minimum absolute increase of 5 mm and the longest diameter should exceed 15mm. Appearance of new lesions

Secondary Outcome Measures

Measure:Conversion rate from Minimal Residual Disease Positive (MRD+) to Minimal Residual Disease Negative (MRD-)
Time Frame:Assessed at day +100 (prior to beginning maintenance), 6 months, 1 year and up to 2 years post-BMT
Safety Issue:
Description:Proportion of patients whose whole blood and bone marrow results transition from MRD positive to MRD negative during therapy for up to 2 years post-BMT. An MRD Negative status will be defined as all results from whole blood and BM that are negative for the presence of residual clonal cells (with assay sensitivity of 10^-6) per Adaptive Biotechnologies' reporting methods.
Measure:Minimal Residual Disease (MRD) correlation with Progression Free Survival (PFS)
Time Frame:Assessed at day +100 post BMT (prior to beginning of maintenance), 6 months, 1 year and up to 2 years post-BMT
Safety Issue:
Description:To compare the median PFS for MRD negative population with MRD positive population
Measure:Incidence of Adverse event
Time Frame:Safety assessment will be done throughout the study for approximately 2 years
Safety Issue:
Description:Number of Participants with grade 3,4 or 5 Adverse events/Serious Adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

  • Acalabrutinib
  • Non Hodgkin's lymphoma
  • Blood or Marrow transplant
  • BMT
  • Maintenance therapy
  • Bruton's Tyrosine Kinase Inhibitor

Last Updated

August 12, 2020