A Phase 3, Randomized, Open-Label, Controlled, Multicenter Study of Zandelisib (ME-401) in Combination with Rituximab Versus Standard Immunochemotherapy in Patients with Relapsed Indolent Non-Hodgkin*s Lymphoma (iNHL) - The COASTAL Study
- Conditions
- cancer from white blood cellsLymph node cancer. Recurringslow growing10025322
- Registration Number
- NL-OMON51210
- Lead Sponsor
- MEI Pharma Inc.
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 1
1. Male or female subjects >=18 years of age, >=19 years in Korea, or >=20 years
for subjects in Japan and Taiwan, at time of signing informed consent
2. Histologically confirmed diagnosis of CD20 positive iNHL with histological
subtype limited to:
a. FL Gr 1, Gr 2, or Gr 3a
b. MZL (splenic, nodal, or extra-nodal)
[Histopathological report confirming diagnosis must be available during
screening procedures]
3. Subjects with relapsed or refractory disease who received >=1 prior lines of
therapy that must have included an anti-CD20 antibody in combination with
cytotoxic chemotherapy or L, with or without subsequent maintenance therapy. [A
line of therapy is defined as following: a minimum of 2 consecutive cycles of
immunochemotherapy or R-L, at least 4 doses of anti-CD20 mAb (R) single agent
therapy a minimum of 2 consecutive cycles of therapy with an investigational
agent. Maintenance therapy given after an induction treatment (e.g., R
maintenance) is considered as the same line of therapy]. [Please seeExclusion
Criteria #2 for further clarification]. Relapsed or refractory disease defined
as:
• Relapsed disease: disease progression after a response (complete response
[CR] or partial response [PR]) lasting >=6 months
• Refractory disease: no response to therapy (no CR or PR) or response lasting
<6 months
4. Subjects must have at least one bi-dimensionally measurable nodal lesion
with the longest diameter > 1.5 cm and/or an extranodal lesion >1.0 cm in the
longest diameter (that has not been previously irradiated) according to the
Lugano Classification
5. Adequate hematologic parameters at screening unless abnormal values are due
to disease per Investigator assessment:
• Absolute neutrophil count (ANC) >=1.0 × 109/L (>=1,000/mm3)
• Platelet count >=75.0 × 109/L (>=75,000/mm3)
• Hemoglobin >=9 g/dL
6. Adequate renal and hepatic function per local laboratory reference range at
screening as follows:
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <=1.5 × upper
limit of normal (ULN)
• Total bilirubin <=2.0 × ULN or <=3 × ULN for subjects with Gilbert-Meulengracht
syndrome
• Estimated glomerular filtration rate (eGFR) >50 mL/min using the
Cockcroft-Gault equation (Appendix 2)
7. QT-interval corrected according to Fridericia*s formula (QTcF) <=450 msec;
subjects with QTc >450 msec but <480 msec may be enrolled provided the
QTc prolongation is due to a right bundle branch block (RBBB), left bundle
branch block (LBBB), or pacemaker and is confirmed stable by a cardiologist.
8. Left ventricular ejection fraction (LVEF) >=45% as measured by echocardiogram
(ECHO) or multi-gated acquisition scan. [If LVEF <45% by ECHO, a repeat
measurement can be conducted within the screening period.]
9. Subjects must have completed any prior systemic anti-cancer treatment >=4
weeks (or >=5 times the half-life [t*] of used therapeutics [including
investigational therapy], whichever is longer) or radiation therapy >=2 weeks
before study D1, and >=3 months before study D1 for high dose therapy with stem
cell transplantation, radioimmunotherapy, and CAR T-cell therapy.
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
11. Life expectancy of at least 3 months
12. All AEs and laboratory toxicities related to prior therapy must res
1. Histologically confirmed diagnosis of FL Gr 3b or transformed disease
• For subjects with clinical signs of rapid disease progression (e.g., marked
B-symptoms), and laboratory or radiographic indication (e.g., high lactate
dehydrogenase level or standardized uptake value by PET), a fresh biopsy is
recommended to rule out transformed disease
2. Subjects who received both R/O-B and R/O-CHOP (or other
anthracycline-containing regimen) as previous lines of therapy, and those who
received only single agent anti-CD20 mAb therapy as prior line of treatment
3. Prior therapy with PI3K inhibitors
4. Ongoing or history of drug-induced pneumonitis
5. Known lymphomatous involvement of the central nervous system
6. Seropositive for or active viral infection with hepatitis B virus:
• HBsAg positive
• HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable
viral DNA by PCR
[Note: Subjects who are HBsAg negative and viral DNA PCR negative are eligible.
These subjects should receive prophylactic therapy for hepatitis as per
institutional standards.]
7. Known seropositive for, or active infection with hepatitis C virus.
• Subjects with positive hepatitis C virus (HCV) antibodies are eligible with
negative PCR test for HCV
8. Known seropositive for, or active and uncontrolled infection with human
immunodeficiency virus (HIV), or with acquired immunodeficiency syndrome
(AIDS), or currently taking medications for HIV that are contraindicated for
concomitant use in this study
9. Known seropositive for, or active infection with human T-cell leukemia virus
type 1
10. Any uncontrolled clinically significant illness including, but not limited
to, active infections requiring systemic antimicrobial therapy, hypertension,
angina, arrhythmias or other uncontrolled cardiovascular condition, pulmonary
disease, autoimmune dysfunction and urinary infection or flow obstruction.
11. Hypersensitivity or other clinically significant reaction to the study drug
or its inactive ingredients or other therapy used in the study
12. Major surgical procedure within 4 weeks prior to study D1 (minor surgical
procedures, e.g., lymph node biopsy, performed within 1 day or with an
overnight stay are allowed)
13. Previous or concurrent cancer that is distinct in primary site or histology
from indolent B cell NHL within 3 years before start of study treatment except
for curatively treated cervical cancer in situ, non-melanoma skin cancer, and
superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ],
and T1 [tumor invades lamina propria]), and asymptomatic localized prostate
cancer with no requirement for systemic therapy or requiring only hormonal
therapy and with normal prostate-specific antigen values within >=12 months
prior to randomization
14. History of clinically significant cardiovascular abnormalities such as
congestive heart failure (New York Heart Association (NYHA) classification >= II
[NYHA 1994]), myocardial infarction within 6 months of study entry.
15. History of clinically significant gastrointestinal (GI) conditions,
particularly:
• Known GI condition that would interfere with swallowing or the oral
absorption or tolerance of study drug
• Pre-existing malabsorption syndrome or other clinical situation that would
affect oral absorption
16. Fem
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS as determined by the IRRC</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Efficacy: ORR and CRR as determined by the IRRC<br /><br>• OS<br /><br>• PRO - time to deterioration in the 9-item DRS-P subset of FlymSI-18<br /><br>• PRO-change from baseline in EQ-5D total score at specified study visits<br /><br>• Treatment-emergent AEs, serious AEs, and laboratory abnormalities</p><br>