Phase 2 Study of ME-401 in Subjects with Follicular Lymphoma
- Conditions
- Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL)MedDRA version: 21.0Level: LLTClassification code 10029473Term: Nodular (follicular) 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)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-002896-17-AT
- Lead Sponsor
- MEI Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 200
1. Age = 18 years (or age of majority)
2. Histologically confirmed diagnosis of FL as defined in the WHO classification scheme, limited to Grade 1, 2, or 3a
3. Histologically confirmed diagnosis as defined in the World Health
Organization (WHO) classification (Swerdlow 2016) of:
a. Follicular lymphoma (FL) limited to Grade 1, 2, or 3a; or
b. Marginal zone lymphoma (MZL), including nodal, extranodal, and
splenic MZL (histopathological report confirming diagnosis must be
available during screening procedures).
4. Subjects with relapsed or refractory FL or MZL who received =2 prior therapy regimens. A previous regimen is defined as one of the following: at least two months of single-agent therapy or at least two consecutive cycles of polychemotherapy, autologous transplant, or radioimmunotherapy. Prior therapy must include an anti-CD20 monoclonal antibody (mAb) and an alkylating agent(s). Relapsed or refractory disease defined as:
a. Relapsed disease: disease progression after a response (CR or PR) lasting =6 months
b. Refractory disease: no response to therapy (no CR or PR) or response lasting < 6 months
5. At least one bi-dimensionally measurable nodal lesion >1.5 cm orextranodal lesions >1 cm in its longest diameter by computed tomography (CT) scan as defined by the Modified Lugano
Classification(Appendix 5).
a. Previously irradiated lesions can be selected as target lesions only in cases of unequivocal evidence of progression.
b. For subjects with splenic MZL only: diffuse spleen involvement with splenomegaly, which is defined as the splenic vertical length greater than 13 cm.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Oken 1982; Appendix 6).
7. Adequate hematologic parameters at screening unless abnormal values are due to lymphoma per Investigator assessment:
a. Absolute neutrophil count (ANC) =1.0 × 109/L (= 1,000/mm3)
b. Platelet count =75.0 × 109/L (= 75,000/mm3)
8. Adequate renal and hepatic function per local laboratory reference range at screening as follows:
a. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamicpyruvate transaminase (SGPT) =3.0 × upper limit of normal(ULN)
b. Total bilirubin =2.0 × ULN or =3 × ULN for subjects with Gilbert's syndrome
c. Serum creatinine =1.5 × ULN or estimated glomerular filtration rate (eGFR) >50 mL/min using the Cockcroft-Gault equation (Appendix 2)
9. QT-interval corrected according to Fridericia's formula (QTcF) =450 milliseconds (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.
10. Left ventricular ejection fraction (LVEF) = 45% as measured by echocardiogram or multigated acquisition scan (MUGA). If LVEF <45% by ECHO, a repeat measurement can be conducted within the screening period.
11. Subjects must have completed any prior systemic anti-cancer treatment within =4 weeks of Cycle 1 Day 1 (or =5 times the half-life [t½], whichever is longer); =8 weeks for antibody agents; =2 weeks for radiation therapy; and =3 months for high dose therapy with stem cell transplantation or CAR T cell therapy or radioimmunotherapy.
12. All adverse events and laboratory toxicities related to prior therapy must resolve to Grade =1 prior to the start of the study therapy (unless otherwise specified in eligibility criteria).
13
1. Histologically confirmed FL Grade 3b, or transformed disease (assessed by the Investigator):
a. For patients with clinical (e.g., marked B-symptoms), laboratory (e.g., high lactate dehydrogenase [LDH]) or radiographic (e.g., high standardized uptake value by positron emission tomography [PET]) signs of rapid disease progression, a fresh tumor biopsy prior to enrollment is required to rule out transformed disease
2. Known lymphomatous involvement of the central nervous system.
3. Major surgical procedure within 4 weeks prior to study Day 1 (minor surgical procedures, [e.g., lymph node biopsy] performed within 1 day or with an overnight stay are allowed).
4. Prior therapy with PI3K inhibitors.
5. Any uncontrolled clinically significant illness including, but not limited to, active infections requiring systemic antimicrobial therapy, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
6. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody plus have a positive hepatitis B PCR assay; subjects with a negative PCR assay are permitted with appropriate anti-viral prophylaxis
7. Positive HCV Ab; subjects with positive hepatitis C antibody are eligible if they are negative for HCV by PCR
8. Known history of, or active human immunodeficiency virus (HIV) infection.
9. Ongoing or history of drug-induced pneumonitis
10. 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 enrollment.
11. History of clinically significant cardiovascular abnormalities such as congestive heart failure (New York Heart Association classification = II [NYHA 1994]), myocardial infarction within 6 months of study entry.
12. History of clinically significant gastrointestinal (GI) conditions, particularly:
a. Known GI condition that would interfere with swallowing or the oral absorption or tolerance of study drug
b. Pre-existing malabsorption syndrome or other clinical situation that would affect oral absorption
13. Females who are pregnant; females who plan to breastfeed during study treatment through 90 days after ending treatment.
14. Psychiatric illness/social situations that would interfere with study compliance.
15. Hypersensitivity or other clinically significant reaction to the study drug or its inactive ingredients.
16. Any other condition for which, in the opinion of the Investigator, participation would not be in the best interest of the subject.
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