A phase 2 trial to study safety and efficacy of Capivasertib in patients with blood cancer where disease or cancer cell grows after a period of remission or response to treatment does not last very long
- Conditions
- Relapsed or Refractory B-cell Non-Hodgkin LymphomaMedDRA version: 24.0Level: LLTClassification code 10067070Term: Follicular B-cell non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10061275Term: Mantle cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-000870-27-ES
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 272
- Patient must be >/= 18 years of age, at the time of signing the informed consent
- ECOG performance status - Life expectancy > 6 months
- Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing
Additional core inclusion criteria may apply, please refer to the protocol.
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 PR) after at least 2 prior systemic lines of therapy (including anti-CD20mAb and an alkylating agent)
4. Patients 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 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. Patients 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. Patients 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 177
- 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 patient has been disease free for >/= 2 years
- With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy >/= CTCAE Grade 2 at the time of starting study treatment
- Known medically apparent CNS lymphoma or leptomeningeal disease
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values at screening:
a) Absolute neutrophil count < 1.0 × 10^9/L; < 0.75 × 10^9/L in participants with known bone marrow involvement of malignant disease
b) Platelets < 75 × 10^9/L; < 50 × 10^9/L in participants with known bone marrow involvement of malignant disease
c) 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:
a) 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
b) 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.
c) Prior allogenic 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, CAR-T therapy) and/or autologous HSCT within 3 months from the first dose of capivasertib.
d) Receipt of live, attenuated vaccine within 28 days before the first dose of study treatment(s).
e) Patients who, due to other medical conditions /prior history /concomitant medications are, in the investigator's opinion, at a risk of a 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 patients with blastoid or pleiomorphic variant or documented TP53 mutation at study entry/most recent relapse.
4. Patients who, in the Investigator’s opinion, require immediate cytoreductive therapy for disease control
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method