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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03932331
Recruitment Status : Recruiting
First Posted : April 30, 2019
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
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 Drug: Acalabrutinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 29, 2020
Estimated Primary Completion Date : March 25, 2022
Estimated Study Completion Date : August 25, 2022


Arm Intervention/treatment
Experimental: Acalabrutinib
Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.
Drug: Acalabrutinib
Acalabrutinib 100 mg orally twice daily




Primary Outcome Measures :
  1. Phase 1: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 years. ]
  2. Phase 2: Overall Response Rate (ORR) [ Time Frame: up to 3 years ]
  3. Phase 1: Pharmacokinetics Characterization after single dose, AUC (Area under the plasma concentration-time curve (from zero to infinity) ) [ Time Frame: approximately 1 month. ]
  4. 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. ]
  5. 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. ]
  6. Phase 1: Pharmacokinetics Characterization after single dose, Cmax (Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  7. Phase 1: Pharmacokinetics Characterization after single dose, tmax (Time to maximum concentration) [ Time Frame: approximately 1 month. ]
  8. Phase 1: Pharmacokinetics Characterization after single dose, CL/F (Oral clearance) [ Time Frame: approximately 1 month. ]
  9. Phase 1: Pharmacokinetics Characterization after single dose, Vz/F (Volume of distribution) [ Time Frame: approximately 1 month. ]
  10. Phase 1: Pharmacokinetics Characterization after single dose, λz (Terminal rate constant) [ Time Frame: approximately 1 month. ]
  11. Phase 1: Pharmacokinetics Characterization after single dose, t1/2 (Terminal half life) [ Time Frame: approximately 1 month. ]
  12. Phase 1: Pharmacokinetics Characterization after single dose, MR_Cmax (metabolite-to-parent ratio, Maximum observed plasma concentration) [ Time Frame: approximately 1 month. ]
  13. 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. ]
  14. 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. ]
  15. Phase 1: Pharmacokinetics Characterization after multiple doses, Cmax,ss (Maximum observed plasma concentration at steady state) [ Time Frame: approximately 1 month. ]
  16. Phase 1: Pharmacokinetics Characterization after multiple doses, Cmin,ss (Minimum observed plasma drug concentration at steady state) [ Time Frame: approximately 1 month. ]
  17. Phase 1: Pharmacokinetics Characterization after multiple doses, tmax,ss (Time to maximum concentration at steady stage) [ Time Frame: approximately 1 month. ]
  18. Phase 1: Pharmacokinetics Characterization after multiple doses, CLss/F (Oral clearance at steady stage) [ Time Frame: approximately 1 month. ]
  19. 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. ]
  20. 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. ]
  21. Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(AUC) (Accumulation ratio calculated as AUCτ(steady state)/AUCτ(first dose)) [ Time Frame: approximately 1 month. ]
  22. Phase 1: Pharmacokinetics Characterization after multiple doses, Rac(Cmax) (Accumulation ratio calculated as Cmax,ss/Cmax) [ Time Frame: approximately 1 month. ]

Secondary Outcome Measures :
  1. 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. ]
  2. Phase 2: Number of participants with Adverse Events (AEs) [ Time Frame: approximately 2 year. ]
  3. Phase 2: Plasma concentration of acalabrutinib and its major metabolite (sparse sampling) [ Time Frame: up to 1 month. ]
  4. Phase 2: Progression free survival (PFS) [ Time Frame: up to 3 years ]
  5. Phase 2: Duration of Response (DoR) [ Time Frame: up to 3 years ]
  6. Phase 2: Time To Response (TTR) [ Time Frame: up to 3 years ]
  7. Phase 2: Overall Survival (OS) [ Time Frame: up to 3 years ]
  8. Phase 2: Time to Next Treatment (for R/R CLL only) [ Time Frame: up to 3 years ]
  9. Phase 2: Minimum Residual Disease Rate (for R/R CLL only) [ Time Frame: up to 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03932331


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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China
Research Site Not yet recruiting
Beijing, China, 100044
Research Site Recruiting
Beijing, China, 100142
Research Site Not yet recruiting
Beijing, China, 100191
Research Site Not yet recruiting
Changchun, China, 130021
Research Site Not yet recruiting
Changsha, China, 410008
Research Site Not yet recruiting
Changzhou, China, 272100
Research Site Withdrawn
Chengdu, China, 610041
Research Site Not yet recruiting
Chengdu, China, 610041
Research Site Not yet recruiting
Dalian, China, 116027
Research Site Not yet recruiting
Fuzhou, China
Research Site Not yet recruiting
Guiyang, China, 550004
Research Site Not yet recruiting
Haikou, China, 570311
Research Site Not yet recruiting
Hangzhou, China, 310003
Research Site Not yet recruiting
Hangzhou, China, 310022
Research Site Not yet recruiting
Harbin, China, 150000
Research Site Not yet recruiting
Harbin, China, 150049
Research Site Not yet recruiting
Hefei, China, 230031
Research Site Not yet recruiting
Hohhot, China, 10050
Research Site Not yet recruiting
Lanzhou, China, 730030
Research Site Not yet recruiting
Nanchang, China, 330006
Research Site Not yet recruiting
Nanjing, China, 210029
Research Site Not yet recruiting
Shanghai, China, 200032
Research Site Not yet recruiting
Shijiazhuang, China, 050035
Research Site Not yet recruiting
Suzhou, China, 215006
Research Site Not yet recruiting
Tianjin, China, 300020
Research Site Not yet recruiting
Tianjin, China, 300060
Research Site Not yet recruiting
Urumqi, China, 830054
Research Site Not yet recruiting
Xining, China, 810007
Research Site Not yet recruiting
Zhengzhou, China, 450008
Research Site Not yet recruiting
Zhengzhou, China, 450052
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Jun Zhu, Prof Beijing Cancer Hospital
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03932331    
Other Study ID Numbers: D8220C00007
2018L02939 ( Registry Identifier: CFDA/ NMPA )
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: May 7, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin