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Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)

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ClinicalTrials.gov Identifier: NCT05008055
Recruitment Status : Recruiting
First Posted : August 17, 2021
Last Update Posted : May 13, 2022
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 19, 2021
First Posted Date  ICMJE August 17, 2021
Last Update Posted Date May 13, 2022
Actual Study Start Date  ICMJE November 3, 2021
Estimated Primary Completion Date November 2, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2022)		 Proportion of participants with objective response [ Time Frame: Until progression of disease [PD] or last evaluable assessment in the absence of progression (Assessed Up to 1.6 Years) ]
Estimation of effectiveness of the capivasertib by assessment of objective response rate (ORR). The ORR is defined as the proportion of participants achieving either complete response (CR) or partial response (PR) according to the Lugano 2014 Classification for NHL as assessed by blinded independent central review (BICR).
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2021)		 Proportion of participants with objective response [ Time Frame: Until progression of disease [PD] (Assessed Up to 1.6 Years) ]
Estimation of effectiveness of the capivasertib by assessment of objective response rate (ORR). The ORR is defined as the proportion of participants achieving either complete response (CR) or partial response (PR) according to the Lugano 2014 Classification for NHL as assessed by blinded independent central review (BICR).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2022)
  • Duration of response (DoR) [ Time Frame: Screening (days -28 to -1), Weeks 8, 16, 24, 36, 48, and 60 and thereafter every 24 weeks for FL/MZL and every 12 weeks for MCL, until PD (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of DoR. The DoR is defined as the time from the date of first documented response until date of documented progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause in the absence of disease progression.
  • Progression-free survival [ Time Frame: Screening (days -28 to -1), Weeks 8, 16, 24, 36, 48, and 60 and thereafter every 24 weeks for FL/MZL and every 12 weeks for MCL, until PD (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of progression-free survival. Progression-free survival is defined as the time from the date of first dose until documented disease progression according to the Lugano 2014 classification for NHL as assessed by BICR, or death due to any cause in the absence of disease progression.
  • Overall survival (OS) [ Time Frame: Until Death due to any cause (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of OS. Overall survival is defined as time from the date of first dose until the date of death due to any cause.
  • Change from baseline in health-related quality of life as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1 and every 4 weeks from Cycle 1 Day 1 for the first 24 weeks and then every 12 weeks thereafter until 12 weeks post progression ]
    Assessment of patient-reported disease-related symptoms, functioning and health-related quality of life as measured by EORTC QLQ-C30.
  • Proportion of participants reporting symptomatic adverse events (AEs) and overall side effect burden at each time point as measured by Patient Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1, every week from Cycle 1 Day 1 for the first 4 weeks, every 4 weeks for the next 8 weeks, and every 12 weeks afterwards until EOT and Post treatment follow-up (Assessed Up to 1.6 Years) ]
    Assessment of patient-reported symptomatic AEs as measured by PGI-TT.
  • Proportion of patients reporting symptomatic AEs and overall side effect burden at each time point as measured by patient-reported outcomes common terminology criteria for adverse events (PRO-CTCAE) [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1, every week from Cycle 1 Day 1 for the first 4 weeks, every 4 weeks for the next 8 weeks, and every 12 weeks afterwards until EOT and Post treatment follow-up (Assessed up to 1.6 Years) ]
    Assessment of patient-reported symptomatic AEs/tolerability of capivasertib as measured by PRO-CTCAE.
  • Time to first subsequent therapy or death (TFST) [ Time Frame: Until first subsequent anti-lymphoma therapy or Death due to any cause (Assessed Up to 1.6 Years ) ]
    Estimation of the effectiveness of capivasertib by TFST. The TFST is defined as time from date of first dose until the start date of first subsequent anti-lymphoma therapy after discontinuation of study treatment or death due to any cause.
  • Time to objective response (TTR) [ Time Frame: From Cycle 1 (28-day treatment cycle) Day 1 until documented response (also until PD/Death for those who never respond) [Assessed Up to 1.6 Years] ]
    Estimation of effectiveness of the capivasertib by assessment of TTR. The TTR is defined as as time from date of first dose until the date of first documented objective response per the Lugano 2014 Classification for NHL as assessed by BICR.
  • Number of participants with AEs and Serious adverse events [ Time Frame: Screening (Day -28 to -1) until Post-treatment follow-up (30 days after last dose) or long-term follow-up (Every 12 weeks) [Assessed up to 1.6 Years] ]
    Assessment of safety and tolerability of the capivasertib.
  • Observed lowest drug concentration reached before the next dose is administered (Ctrough) of capivasertib [ Time Frame: Pre-dose on Cycle 1 (28-day treatment Cycle) Day 1 and on Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 1 Day 22 ]
    Determination of plasma concentration of capivasertib pre-dose (Ctrough).
  • Plasma concentration of capivasertib post-dose [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1: 1 hour, 2 hour and 4 hour post-dose ]
    Determination of plasma concentration of capivasertib post-dose
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2021)
  • Duration of response (DoR) [ Time Frame: Screening (days -28 to -1), Weeks 8, 16, 24, 36, 48, and 60 and thereafter every 24 weeks for FL/MZL and every 12 weeks for MCL, until PD (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of DoR. The DoR is defined as the time from the date of first documented response until date of documented progression according to the Lugano 2014 Classification for NHL as assessed by BICR, or death due to any cause.
  • Progression-free survival [ Time Frame: Screening (days -28 to -1), Weeks 8, 16, 24, 36, 48, and 60 and thereafter every 24 weeks for FL/MZL and every 12 weeks for MCL, until PD (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of progression-free survival. Progression-free survival is defined as the time from the date of first dose until documented disease progression according to the Lugano 2014 classification for NHL as assessed by BICR, or death due to any cause.
  • Overall survival (OS) [ Time Frame: Until Death due to any cause (Assessed Up to 1.6 Years) ]
    Estimation of effectiveness of the capivasertib by assessment of OS. Overall survival is defined as time from the date of first dose until the date of death due to any cause.
  • Change from baseline in health-related quality of life as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1 and every 4 weeks from Cycle 1 Day 1 for the first 24 weeks and then every 12 weeks thereafter until 12 weeks post progression ]
    Assessment of patient-reported disease-related symptoms, functioning and health-related quality of life as measured by EORTC QLQ-C30.
  • Proportion of participants reporting symptomatic adverse events (AEs) and overall side effect burden at each time point as measured by Patient Global Impression of Treatment Tolerability (PGI-TT) [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1, every week from Cycle 1 Day 1 for the first 4 weeks, every 4 weeks for the next 8 weeks, and every 12 weeks afterwards until EOT and Post treatment follow-up (Assessed Up to 1.6 Years) ]
    Assessment of patient-reported symptomatic AEs as measured by PGI-TT.
  • Change in National Cancer Institute patient-reported outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) symptoms [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1, every week from Cycle 1 Day 1 for the first 4 weeks, every 4 weeks for the next 8 weeks, and every 12 weeks afterwards until EOT and Post treatment follow-up (Assessed up to 1.6 Years) ]
    Assessment of patient-reported symptomatic AEs/tolerability of capivasertib.
  • Time to first subsequent therapy or death (TFST) [ Time Frame: Until first subsequent anti-lymphoma therapy or Death due to any cause (Assessed Up to 1.6 Years ) ]
    Estimation of the effectiveness of capivasertib by TFST. The TFST is defined as time from date of first dose until the start date of first subsequent anti-lymphoma therapy after discontinuation of study treatment or death due to any cause.
  • Time to objective response (TTR) [ Time Frame: From Cycle 1 (28-day treatment cycle) Day 1 until documented response (also until PD/Death for those who never respond) [Assessed Up to 1.6 Years] ]
    Estimation of effectiveness of the capivasertib by assessment of TTR. The TTR is defined as as time from date of first dose until the date of first documented objective response per the Lugano 2014 Classification for NHL as assessed by BICR.
  • Number of participants with AEs and Serious adverse events [ Time Frame: Screening (Day -28 to -1) until Post-treatment follow-up (30 days after last dose) or long-term follow-up (Every 12 weeks) [Assessed up to 1.6 Years] ]
    Assessment of safety and tolerability of the capivasertib.
  • Observed lowest drug concentration reached before the next dose is administered (Ctrough) of capivasertib [ Time Frame: Pre-dose on Cycle 1 (28-day treatment Cycle) Day 1 and on Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 1 Day 22 ]
    Determination of plasma concentration of capivasertib pre-dose (Ctrough).
  • Plasma concentration of capivasertib post-dose [ Time Frame: Cycle 1 (28-day treatment Cycle) Day 1: 1 hour, 2 hour and 4 hour post-dose ]
    Determination of plasma concentration of capivasertib post-dose
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Official Title  ICMJE A Modular Phase II, Open-Label, Multicentre Study to Assess the Efficacy and Safety of Capivasertib in Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL)
Brief Summary This study is an open-label, multicenter Phase II study of capivasertib administered orally in participants with Relapsed or Refractory (R/R) B-cell Non-Hodgkin's Lymphoma (NHL).
Detailed Description The study protocol follows a modular design. The study will investigate the safety and efficacy of capivasertib monotherapy in participants with R/R Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and Mantle Cell Lymphoma (MCL).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Intervention  ICMJE Drug: Capivasertib
Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.
Study Arms  ICMJE Experimental: Capivasertib monotherapy
Participants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity.
Intervention: Drug: Capivasertib
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: August 9, 2021)		 272
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2, 2023
Estimated Primary Completion Date November 2, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participants must be ≥ 18 years of age, at the time of signing the informed consent
  • Eastern Cooperative Oncology Group performance status ≤ 2
  • Life expectancy > 6 months
  • Female participants must not be breast-feeding and must have a negative pregnancy test (serum) prior to start of dosing

Module 1 specific inclusion criteria:

Additional Inclusion Criteria for Cohort 1A (R/R FL):

  1. Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
  2. Current need for systemic treatment based on the Investigator's opinion
  3. Relapsed, progressed or refractory (defined as failure to achieve at least a partial response [PR]) after at least 2 prior systemic lines of therapy (including anti-CD20 monoclonal antibody [mAb] and an alkylating agent)
  4. Bi-dimensionally measurable disease on cross sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis.

Additional Inclusion Criteria for Cohort 1B (R/R MZL):

  1. Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist
  2. Current need for systemic treatment based on the Investigator's opinion
  3. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy (including at least one anti-CD20mAb directed regimen either as monotherapy or as chemoimmunotherapy; Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen)
  4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis

Additional Inclusion Criteria for Cohort 1C (R/R MCL):

  1. Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by investigator or local pathologist
  2. Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy

  3. Participants must have received as prior therapies

    Prior regimens must have included:

    • BTK inhibitor and
    • Anti-CD20mAb therapy
  4. Bi-dimensionally measurable disease on cross sectional imaging by CT or MRI with at least one nodal lesion > 1.5 cm in the long axis or at least one extranodal lesion > 1 cm in long axis

Exclusion Criteria:

  • Prior malignancy (other than the disease under study), except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the participant has been disease free for ≥ 2 years
  • With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy ≥ Common Terminology Criteria for Adverse Events Grade 2 at the time of starting study treatment
  • Known medically apparent central nervous system lymphoma or leptomeningeal disease

  • Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:

    1. Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
    2. Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
    3. Creatinine clearance < 50 mL/min per the Cockcroft and Gault formula
  • Clinically significant abnormalities of glucose metabolism as participants with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment and Glycosylated haemoglobin ≥ 8.0% (63.9 mmol/mol)

  • Prior treatment with any of the following:

    1. Any investigational agents or study drugs from a previous clinical study within 5 half lives or 2 weeks from the first dose of capivasertib in this study
    2. Strong inhibitors or inducers of CYP3A4 within 2 weeks prior to the first dose of study treatment (3 weeks for St John's wort), or drugs that are sensitive to inhibition of CYP3A4 within 1 week prior to the first dose of study treatment
    3. Prior allogenic Haematopoietic stem cell transplant (HSCT) within 6 months from the first dose of capivasertib (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus-host disease and concomitant immune suppressive therapy). Prior cellular therapies (eg, Chimeric antigen receptor T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib
    4. Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s)
    5. Participants who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a venous thromboembolism (VTE) and are not willing to accept the VTE prophylaxis, will be excluded. The initiation of an adequate VTE prophylaxis will be based on treating physician risk/benefit assessment and in agreement with the local management guidelines

Additional exclusion core criteria may apply, please refer to the protocol

Module 1 specific exclusion criteria:

  1. Follicular lymphoma grade 3B
  2. Known transformation to aggressive lymphoma, eg, large cell lymphoma
  3. Participants who, in the Investigator's opinion, require immediate cytoreductive therapy for disease control
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 Canada,   Denmark,   France,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05008055
Other Study ID Numbers  ICMJE D361FC00001
2021-000870-27 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
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 requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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 refer 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 patientlevel 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
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Parexel
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date May 2022

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