Relapsed or Refractory B-cell Non-Hodgkin LymphomaPhase 2CAPITALNCT05008055
Study of Capivasertib in Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
A Phase 2 study testing Capivasertib in people with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma, run by AstraZeneca at 17 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
- What is being tested?
- Capivasertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 3 Nov 2021to 25 Oct 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
- Current need for systemic treatment based on the Investigator's opinion
- 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)
- 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):
- Histologically confirmed MZL including splenic, nodal, and extranodal subtypes as assessed by investigator or local pathologist
- Current need for systemic treatment based on the Investigator's opinion
- 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)
- 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):
- 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
- Relapsed, progressed or refractory (defined as failure to achieve at least a PR) after at least 2 prior systemic lines of therapy
- Participants must have received as prior therapies
- Prior regimens must have included:
- BTK inhibitor and
- Anti-CD20mAb therapy
- 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
Who cannot join
- 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:
- Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
- Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
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- 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:
- 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
- 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
- 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
- Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s)
- 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:
- Follicular lymphoma grade 3B
- Known transformation to aggressive lymphoma, eg, large cell lymphoma
- Participants who, in the Investigator's opinion, require immediate cytoreductive therapy for disease control
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
Spain4 sites
Research Site
Badalona, 08003
Research Site
Barcelona, 8035
Research Site
Madrid, 28040
Research Site
Madrid, 28046
United States3 sites
Research Site
Duarte, California, 91010
Research Site
Houston, Texas, 77030
Research Site
Los Angeles, California, 90095
South Korea3 sites
Research Site
Busan, 49241
Research Site
Seoul, 06351
Research Site
Seoul, 3722
United Kingdom3 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Manchester, M20 4BX
Research Site
Sutton, SM2 5PT
About this study
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)
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).
Read the 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).
- Being tested
- Capivasertib
- Keywords
- Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Capivasertib monotherapy
- Medical subject headings
- Recurrence, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapivasertibDrug
Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.
| Study group | Role | What they receive |
|---|---|---|
| Capivasertib monotherapy | Experimental | Participants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity. Receives: Drug: Capivasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective response rate is defined as the proportion of patients achieving either complete response (CR) or partial response (PR) according to the Lugano 2014 Classification for non-Hodgkin lymphoma (NHL) as assessed by blinded independent central review (BICR).
Measured: First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)
Secondary outcomes (5)
Duration of Response
Duration of response 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.
Measured: First documented response until date of documented progression or data-cut off date (21.6 Months)
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. The analysis included all dosed patients, regardless of whether the patient withdrew from therapy, received another anti lymphoma therapy, or clinically progressed prior to progression according to the Lugano 2014 Classification for NHL.
Measured: First dose until documented disease progression or data cut-off date (21.6 Months)
Overall Survival (OS)
Overall survival is defined as time from the date of first dose until the date of death due to any cause. The analysis included all dosed patients, regardless of whether the patient withdrew from therapy or received another anti lymphoma therapy. Patients who had not died by the analysis DCO date were censored at their last known date of being alive before the DCO date. Patients who were known to be alive or dead after the DCO date were censored at the DCO date. Patients who were lost to follow-up were censored at the date when they were last known to have been alive.
Measured: First dose until data cut-off date (21.6 Months)
Number of Patients With Adverse Events and Serious Adverse Events
The safety and tolerability of the capivasertib treatment in each Cohort was assessed.
Measured: Screening (Day -28 to -1) until Post-treatment follow-up up to 30 days after last dose or long-term follow-up or study completion (Every 12 weeks until death or lost to follow-up, unless patient have withdrawn consent [up to 21.6 Months])
Plasma Concentration of Capivasertib Overtime
The plasma concentration of capivasertib when administered in patients in each Cohort was determined.
Measured: Cycle 1 (28-day treatment Cycle) Day 1 and on Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 1 Day 22 (Pre-dose and post-dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2021
- Study start3 Nov 2021
- Primary completion22 Aug 2023
- Study completion25 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed or Refractory B-cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05008055
- Sponsor's protocol ID
- D361FC00001
- Other IDs
- 2021-000870-27
- Acronym
- CAPITAL
- Status last verified
- Nov 2024
- First submitted
- 19 Jul 2021
- Last updated
- 20 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05008055
- Acronym / sponsor ID
- CAPITAL / D361FC00001
- Keywords
- Follicular Lymphoma, Marginal Zone Lymphoma, Mantle Cell Lymphoma, Capivasertib monotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 3 Nov 2021 (actual)
- Primary completion
- 22 Aug 2023 (actual)
- Study completion
- 25 Oct 2024 (actual)
- First posted
- 17 Aug 2021 (actual)
- Results
- Posted 20 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Capivasertib monotherapy | Experimental | Drug: CapivasertibParticipants with R/R FL, R/R MZL, and R/R MCL will receive capivasertib orally until progression of disease (PD) or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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
- Histologically confirmed diagnosis of FL Grade 1, 2, or 3a as assessed by investigator or local pathologist
Key exclusion criteria (19 listed)
- 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:
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapivasertibCapivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off. | Drug | Capivasertib monotherapy |
Primary outcome
Objective Response Rate
Time frame: First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)
Objective response rate is defined as the proportion of patients achieving either complete response (CR) or partial response (PR) according to the Lugano 2014 Classification for non-Hodgkin lymphoma (NHL) as assessed by blinded independent central review (BICR).
5 secondary outcomes
Duration of Response
Time frame: First documented response until date of documented progression or data-cut off date (21.6 Months)
Progression-free Survival
Time frame: First dose until documented disease progression or data cut-off date (21.6 Months)
Overall Survival (OS)
Time frame: First dose until data cut-off date (21.6 Months)
Number of Patients With Adverse Events and Serious Adverse Events
Time frame: Screening (Day -28 to -1) until Post-treatment follow-up up to 30 days after last dose or long-term follow-up or study completion (Every 12 weeks until death or lost to follow-up, unless patient have withdrawn consent [up to 21.6 Months])
Plasma Concentration of Capivasertib Overtime
Time frame: Cycle 1 (28-day treatment Cycle) Day 1 and on Cycle 1 Day 8, Cycle 1 Day 15 and Cycle 1 Day 22 (Pre-dose and post-dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Redacted Statistical Analysis PlanLink provided by the sponsor.
- Redacted Clinical Study ProtocolLink provided by the sponsor.
- Redacted CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Capivasertib in people with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma, run by AstraZeneca at 17 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Spain, United States, South Korea, United Kingdom, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: First dose until progression of disease [PD] or last evaluable assessment in the absence of progression or data cut-off date (21.6 Months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.