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

Primary Purpose

Mantle Cell Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acalabrutinib
Sponsored by
SCRI Development Innovations, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring Acalabrutinib, Non Hodgkin's lymphoma, Blood or Marrow transplant, BMT, Maintenance therapy, Bruton's Tyrosine Kinase Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Colorado Blood Cancer Institute
  • Tulane University, Office of Clinical Research
  • HCA Midwest
  • Tennessee Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acalabrutinib

Arm Description

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

Outcomes

Primary Outcome Measures

Progression Free Survival Rate (PFS)
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

Conversion rate from Minimal Residual Disease Positive (MRD+) to Minimal Residual Disease Negative (MRD-)
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.
Minimal Residual Disease (MRD) correlation with Progression Free Survival (PFS)
To compare the median PFS for MRD negative population with MRD positive population
Incidence of Adverse event
Number of Participants with grade 3,4 or 5 Adverse events/Serious Adverse events

Full Information

First Posted
May 15, 2020
Last Updated
January 13, 2023
Sponsor
SCRI Development Innovations, LLC
Collaborators
Acerta Pharma, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04402138
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 7, 2020 (Actual)
Primary Completion Date
August 7, 2027 (Anticipated)
Study Completion Date
August 7, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SCRI Development Innovations, LLC
Collaborators
Acerta Pharma, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
Acalabrutinib, Non Hodgkin's lymphoma, Blood or Marrow transplant, BMT, Maintenance therapy, Bruton's Tyrosine Kinase Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acalabrutinib
Arm Type
Experimental
Arm Description
Acalabrutinib will be self-administered orally for up to approximately 2 years post-BMT.
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
Calquence
Intervention Description
Acalabrutinib 100 mg BID will be self-administered orally starting from 100 day (+/- 7 days) Post-BMT on a 28-day schedule, with or without food, until the patient has reached approximately 2 years post-BMT.
Primary Outcome Measure Information:
Title
Progression Free Survival Rate (PFS)
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
Time Frame
Assessed with CT/MRI/FGD-PET scans for up to 24 months
Secondary Outcome Measure Information:
Title
Conversion rate from Minimal Residual Disease Positive (MRD+) to Minimal Residual Disease Negative (MRD-)
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.
Time Frame
Assessed at day +100 (prior to beginning maintenance), 6 months, 1 year and up to 2 years post-BMT
Title
Minimal Residual Disease (MRD) correlation with Progression Free Survival (PFS)
Description
To compare the median PFS for MRD negative population with MRD positive population
Time Frame
Assessed at day +100 post BMT (prior to beginning of maintenance), 6 months, 1 year and up to 2 years post-BMT
Title
Incidence of Adverse event
Description
Number of Participants with grade 3,4 or 5 Adverse events/Serious Adverse events
Time Frame
Safety assessment will be done throughout the study for approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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. Men and women ≥18 years-of-age at the time of signature of the informed consent form (ICF). 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. Subject must have completed induction chemotherapy and plan to and be eligible to receive their first BMT per standard of care. Availability of an archival paraffin-embedded tumor block for MRD testing. The Investigator anticipates that the subject will meet the appropriate lab requirements listed in Screening #2 by Day 100. Patients who received prior therapy with a BTK inhibitor are eligible to enroll. Inclusion Criteria Post-BMT, Prior to Day 100 (Screening #2): 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 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. 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. 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 (PHI). Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Subjects who have relapsed or progressed at any time prior to BM Subjects with known mutations that confer resistance to a BTK inhibitor. Confirmed clinical PD since the time of BMT 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. 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. 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. 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. Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components). Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease). Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura. Requires treatment with a strong CYP3A4 inhibitor/inducer 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. Prothrombin time (PT)/ international normalized ratio (INR) or activated partial thromboplastin time (aPTT) >2 x ULN (in the absence of lupus anticoagulant). 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. History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug. 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. 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. Breastfeeding or pregnant. Concurrent participation in another therapeutic clinical trial. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol. The inability to swallow capsules.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian Flinn, MD, PhD
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Tulane University, Office of Clinical Research
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
HCA Midwest
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64132
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37302
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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