Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02928419
• Date of registration: 05/10/2016
• Prospective Registration: No
• Primary sponsor: Associazione Qol-one
• Public title: Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q
• Scientific title: Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q: a Multicenter, Randomized, Double-blind, Placebo Controlled Study - QOL-ONE Rev2MDS
• Date of first enrolment: May 2015
• Target sample size: 2
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02928419
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

France, Greece, Italy

Contacts

• Name: Esther Natalie Oliva, MD
• Affiliation: QOL-ONE Associazione Culturale e di Ricerca

Key inclusion & exclusion criteria

Inclusion Criteria:

- Adult subjects (18 years of age or older) with MDS and low or intermediate-1 IPSS risk
and del5q as a single abnormality, at the time of their screening and enrollment into
the study

- Subjects must not have received any prior treatment course with any immunomodulating
agent nor TPO-R agonists

- Subjects must be dependent on regular packed RBC transfusions, as defined by
international working group 2006 criteria, and must have a PLT count taken within the
4 weeks prior to screening that is >25 Gi/L.

- Absolute Neutrophil Counts (ANC) = 0.5 GiL

- Resistant or refractory to erythropoetic stimulating agents (ESAs) and/or serum
erythropoetin levels > 500 miU/L

- Subjects must be ineligible or relapsed or refractory to receive treatment options of
azacitidine and decitabine.

- Subjects must have PLT count and RBC and PLT transfusion data available over a period
of 8 weeks prior to screening.

- During the 2 months prior to randomization, subjects must have a baseline BM
examination including all of the following: cytomorphology, cytogenetics and histology

- ECOG Performance Status must be 0-3.

- The following clinical chemistries MUST NOT exceed the upper limit of normal (ULN)
reference range: creatinine, ALT, AST, total bilirubin (except for Gilbert's
Syndrome), gamma-gt and alkaline phosphatase. In addition, albumin must not be below
the lower limit of normal (LLN) by more than 10%.

- If subject meets the criteria for childbearing potential:

1. Negative pregnancy test in female subjects within the 3 days prior to Day 1 of
1st cycle and effective contraception for at least 4 weeks.

2. Subject is practicing an acceptable method of contraception (documented in
chart). Female subjects (or female partners of male subjects) must either be of
non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal
ligation or post-menopausal >1 year), or of childbearing potential and use of an
highly effective method of contraception from 2 weeks prior to administration of
study medication, throughout the study, and 28 days after completion or premature
discontinuation from the study.

- Criteria for women of non-childbearing potential: A female patient or a female partner
of a male patient is considered to have childbearing potential unless she meets at
least one of the following criteria:

1. Age = 50 years and naturally amenorrhoeic for = 1 year (amenorrhoea following
cancer therapy or during lactation does not rule out childbearing potential).

2. Premature ovarian failure confirmed by a gynaecologist

3. Previous bilateral salpingo-oophorectomy, or hysterectomy

4. XY genotype, Turner syndrome, uterine agenesis.

- Subject is able to understand and comply with protocol requirements and instructions.

- Subject has signed and dated informed consent.

Exclusion Criteria:

- MDS with intermediate-2 or high IPSS risk

- Additional cytogenetic abnormalities

- Transfusion independence (TI) by IWG 2006 criteria

- Absolute Neutrophil Count < 0.5 Gi/L and/or Platelet counts < 25 Gi/L

- History of treatment for cancer with systemic chemotherapy and/or radiotherapy within
the last 2 years

- History of treatment with immunomodulatory drugs or other TPO-R agonists.

- Thrombophilia, pre-existing history of thrombosis, cardiovascular disease (including
congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or
arrhythmia known to increase the risk of thromboembolic events (e.g. atrial
fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with
Bundle Branch Block)

- Bone Marrow fibrosis that leads to an inability to aspirate marrow for assessment.

- Leukocytosis >=25,000/uL prior to Day 1 of study medication.

- Monocytosis > 1000/ uL prior to Day 1 of study medication.

- Female subjects who are nursing or pregnant (positive serum or urine Beta-human
chorionic gonadotropin [B-hCG] pregnancy test).

- Women of childbearing potential unless all of the conditions of the Pregnancy
Prevention Programme illustrated in sections 6.4 are met (see sections 6.4).

- Known hypersensitivity to lenalidomide.

- Current alcohol or drug abuse.

- Treatment with an Investigational Product within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.

- Active and uncontrolled infections.

- Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndromes

Intervention(s)

Drug: Eltrombopag/Revolade

Drug: Lenalidomide

Other: Placebo

Primary Outcome(s)

Response (patients number with composite endpoint experience) [Time Frame: 24 weeks]

Secondary Outcome(s)

Hb changes [Time Frame: 24 weeks]

Overall survival [Time Frame: 36 months]

Progression free survival [Time Frame: 36 months]

Response (patients number with composite endpoint experience on long-term) [Time Frame: 36 months]

Duration of cytogenetic response [Time Frame: 36 months]

Quality of Life (QOL) [Time Frame: 36 months]

Cytogenetic responses [Time Frame: 36 months]

Erythroid response [Time Frame: 36 months]

Safety (number of adverse events) [Time Frame: 36 months]

Secondary ID(s)

QOL-ONE Rev2MDS

Source(s) of Monetary Support

Please refer to primary and secondary sponsors