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Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies

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ClinicalTrials.gov Identifier: NCT03932331
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : July 1, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE April 16, 2019
First Posted Date  ICMJE April 30, 2019
Last Update Posted Date July 1, 2020
Actual Study Start Date  ICMJE April 29, 2020
Estimated Primary Completion Date March 25, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
  • Phase 1: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 years. ]
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: up to 3 years ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) ) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC0-12 (Area under the plasma concentration-time curve (from zero to 12 hours)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC0-t (Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, MR_AUC (metabolite-to-parent ratio, Area under the plasma concentration-time curve (from zero to infinity)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, AUCτ,ss (Area under the plasma concentration-time curve across the dosing interval at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, MR_ AUCτ (metabolite-to-parent ratio, Area under the plasma concentration-time curve across the dosing interval) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, TCP (Temporal change parameter in systemic exposure (also known as: time dependency, temporal parameter change, linearity index); calculated as AUCτ(steady state)/AUC(first dose)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax) [ Time Frame: approximately 1 month. ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Phase 1: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 years. ]
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: up to 2 years. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) ) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC0-12 (Area under the plasma concentration-time curve (from zero to 12 hours)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, AUC0-t (Area under the plasma concentration-time curve (from zero to the time of the last measurable concentration)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after single dose, MR_AUC (metabolite-to-parent ratio, Area under the plasma concentration-time curve (from zero to infinity)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, AUCτ,ss (Area under the plasma concentration-time curve across the dosing interval at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, MR_ AUCτ (metabolite-to-parent ratio, Area under the plasma concentration-time curve across the dosing interval) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, TCP (Temporal change parameter in systemic exposure (also known as: time dependency, temporal parameter change, linearity index); calculated as AUCτ(steady state)/AUC(first dose)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose)) [ Time Frame: approximately 1 month. ]
  • Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax) [ Time Frame: approximately 1 month. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2019)
  • Phase 1: Tumor response (number of patients with Complete Response (CR), Partial Response (PR), Stable Diseaase (SD), Progression of Disease (PD)) [ Time Frame: up to 2 years. ]
  • Phase 2: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 year. ]
  • Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling) [ Time Frame: up to 1 month. ]
  • Phase 2: Progression free survival (PFS) [ Time Frame: up to 3 years ]
  • Phase 2: Duration of Response (DoR) [ Time Frame: up to 3 years ]
  • Phase 2: Time To Response (TTR) [ Time Frame: up to 3 years ]
  • Phase 2: Overall Survival (OS) [ Time Frame: up to 3 years ]
  • Phase 2: Time to Next Treatment (for R/R CLL only) [ Time Frame: up to 3 years ]
  • Phase 2: Minimum Residual Disease Rate (for R/R CLL only) [ Time Frame: up to 3 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Phase 1: Tumor response (number of patients with Complete Response (CR), Partial Response (PR), Stable Diseaase (SD), Progression of Disease (PD)) [ Time Frame: up to 2 years. ]
  • Phase 2: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 year. ]
  • Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling) [ Time Frame: up to 1 month. ]
  • Phase 2: Progression free survival (PFS) [ Time Frame: up to 2 years ]
  • Phase 2: Duration of Response (DoR) [ Time Frame: up to 2 years ]
  • Phase 2: Time To Response (TTR) [ Time Frame: up to 2 years ]
  • Phase 2: Overall Survival (OS) [ Time Frame: up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies
Official Title  ICMJE A Phase 1/2 Open Label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Clinical Efficacy of Acalabrutinib in Chinese Adult Subjects With Relapsed or Refractory Mantle Cell Lymphoma, Chronic Lymphocytic Leukemia or Other B-cell Malignancies
Brief Summary This is an open-label, two-part study to assess the safety, tolerability, pharmacokinetics and clinical efficacy of acalabrutinib in Chinese adult subjects with R/R MCL, CLL and other B-cell malignancies. The study is divided into 2 parts: Phase 1 portion and Phase 2 portion.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Phase I: Relapsed or Refractory B-cell Malignancies
  • Phase II Cohort A: Relapsed or Refractory Mantle Cell Lymphoma
  • Phase II Cohort B: Relapsed or Refractory Chronic Lymphocytic Leukemia
Intervention  ICMJE Drug: Acalabrutinib
Acalabrutinib 100 mg orally twice daily
Study Arms  ICMJE Experimental: Acalabrutinib
Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.
Intervention: Drug: Acalabrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 26, 2019)
105
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
45
Estimated Study Completion Date  ICMJE July 26, 2022
Estimated Primary Completion Date March 25, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
  2. Chinese subjects at least 18 years of age at the time of study entry.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
  4. Adequate hematological and organ function.
  5. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy.
  6. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14) (q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers (eg, CD5, CD19, CD20, PAX5). Disease had relapsed after or been refractory to previous treatment.
  7. Diagnosis of CLL that meets published diagnostic criteria. Must have received ≥ 1 prior systemic therapies for CLL.
  8. Active disease per iwCLL 2018 criteria that requires treatment. (CLL only)
  9. Other relapsed/refractory B-cell malignancies without stand of care (phase 1 only).

Exclusion criteria

  1. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject had been disease free for ≥2 years or which would not have limited survival to <2 years.
  2. Significant cardiovascular disease.
  3. Known central nervous system involvement of lymphoma/leukemia or leptomeningeal disease.
  4. Known history of HIV, serologic status reflecting active hepatitis B or C infection.
  5. Major surgery within 4 weeks before first dose of study drugs.
  6. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  7. Required or received anticoagulation with warfarin or equivalent vitamin K antagonist (eg, phenprocoumon).
  8. Prior exposure to a BCR or BCL-2 inhibitor.
  9. Use of a strong inhibitor or inducer of CYP3A.
  10. Breastfeeding or pregnant.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03932331
Other Study ID Numbers  ICMJE D8220C00007
2018L02939 ( Registry Identifier: CFDA/ NMPA )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jun Zhu, Prof Beijing Cancer Hospital
PRS Account AstraZeneca
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP