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

NCT ID: NCT05008055

Last Updated: 2024-12-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-03

Study Completion Date

2024-10-25

Brief Summary

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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

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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).

Conditions

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Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Keywords

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Follicular Lymphoma Marginal Zone Lymphoma Mantle Cell Lymphoma Capivasertib monotherapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Capivasertib

Intervention Type DRUG

Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.

Interventions

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Capivasertib

Capivasertib will be taken orally twice a day (BD) 4 days on/ 3 days off.

Intervention Type DRUG

Eligibility Criteria

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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



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.


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


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


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
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Duarte, California, United States

Site Status

Research Site

Los Angeles, California, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Victoria, British Columbia, Canada

Site Status

Research Site

Aarhus N, , Denmark

Site Status

Research Site

Poitiers, , France

Site Status

Research Site

Villejuif, , France

Site Status

Research Site

Busan, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Badalona, , Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Madrid, , Spain

Site Status

Research Site

Cambridge, , United Kingdom

Site Status

Research Site

Manchester, , United Kingdom

Site Status

Research Site

Sutton, , United Kingdom

Site Status

Countries

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United States Canada Denmark France South Korea Spain United Kingdom

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2021-000870-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D361FC00001

Identifier Type: -

Identifier Source: org_study_id