Clinical Trials /

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

NCT05008055

Description:

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).

Related Conditions:
  • Grade 1 Follicular Lymphoma
  • Grade 2 Follicular Lymphoma
  • Grade 3 Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: D361FC00001
  • SECONDARY ID: 2021-000870-27
  • NCT ID: NCT05008055

Conditions

  • Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CapivasertibCapivasertib monotherapy

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Capivasertib monotherapyExperimentalParticipants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity.
  • Capivasertib

Eligibility Criteria

        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
             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-CD20mAb and an alkylating agent)

          4. Participants should have received up to a maximum of 5 lines of prior therapies.

          5. 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. Participants should have received up to a maximum of 5 lines of prior therapies

          5. 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 should have received up to a maximum of 4 lines of prior therapies

             Prior regimens must have included:

               -  BTK inhibitor and

               -  Anti-CD20 monoclonal antibody 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. Potent inhibitors or inducers of CYP3A4 and/or UGT2B7 within 2 weeks prior to the
                  first dose of study treatment (3 weeks for St John's wort), or sensitive
                  substrates of CYP3A4, CYP2C9 and/or CYP2D6 with a narrow therapeutic window
                  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. MCL participants with blastoid or pleiomorphic variant or documented tumour protein 53
             mutation at study entry/most recent relapse

          4. Participants who, in the Investigator's opinion, require immediate cytoreductive
             therapy for disease control
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of participants with objective response
Time Frame:Until progression of disease [PD] (Assessed Up to 1.6 Years)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:Until Death due to any cause (Assessed Up to 1.6 Years)
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:Assessment of patient-reported disease-related symptoms, functioning and health-related quality of life as measured by EORTC QLQ-C30.
Measure: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)
Safety Issue:
Description:Assessment of patient-reported symptomatic AEs as measured by PGI-TT.
Measure: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)
Safety Issue:
Description:Assessment of patient-reported symptomatic AEs/tolerability of capivasertib.
Measure: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 )
Safety Issue:
Description: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.
Measure: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]
Safety Issue:
Description: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.
Measure: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]
Safety Issue:
Description:Assessment of safety and tolerability of the capivasertib.
Measure: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
Safety Issue:
Description:Determination of plasma concentration of capivasertib pre-dose (Ctrough).
Measure: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
Safety Issue:
Description:Determination of plasma concentration of capivasertib post-dose

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Mantle Cell Lymphoma
  • Capivasertib monotherapy

Last Updated

August 17, 2021