Phase 2 Study of ME-401 in Subjects with Follicular Lymphoma

Phase 1

• Conditions: Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL); MedDRA version: 24.0Level: 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-DE
• Lead Sponsor: MEI Pharma, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-04-10
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

1. Signed informed consent.
2. Age =18 years (or age of majority).
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 is 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 or
extranodal 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. For females of childbearin

Exclusion Criteria

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
polymerase chain reaction (PCR) assay; subjects who have previously
tested positive with a negative PCR assay are permitted with appropriate
anti-viral prophylaxis.
7. Positive hepatitis C virus antibody (HCV Ab); subjects with positive
HCV Ab 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, nonmelanoma
skin cancer, 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