Clinical trial NCT05008055: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
Keywords: Follicular Lymphoma
Marginal Zone Lymphoma
Mantle Cell Lymphoma
Capivasertib monotherapy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2021-08-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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 (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

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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:
measure: Duration of Response
timeFrame: First documented response until date of documented progression or data-cut off date (21.6 Months)
measure: Progression-free Survival
timeFrame: First dose until documented disease progression or data cut-off date (21.6 Months)
measure: Overall Survival (OS)
timeFrame: First dose until data cut-off date (21.6 Months)
measure: Number of Patients With Adverse Events and Serious Adverse Events
timeFrame: 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])
measure: Plasma Concentration of Capivasertib Overtime
timeFrame: 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)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Houston
country: United States
facility: Research Site
state: Texas
city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Aarhus N
country: Denmark
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
References: