Evaluation of ETC-1907206 With Dasatinib in Advanced Haematologic Malignancies

Withdrawn before enrolling · Phase 1

Conditions studied: Ph+ Acute Lymphoblastic Leukemia (Ph+ALL), Ph- Acute Lymphoblastic Leukemia (Ph-ALL), Chronic Myeloid Leukemia Accelerated Phase (CML-AP, Ph+), Chronic Myeloid Leukemia Blast Crisis (CML-BC, Ph+)

In brief

This study evaluates the use of ETC-1907206 in combination with dasatinib in certain types of blood cancers. The first phase of the study (1A) is designed to find the highest tolerated dose of ETC-1907206, while the second phase (1B) will assess the safety and tolerability of the recommended dose of ETC-1907206. ETC-1907206 has been designed to block the activity of an enzyme of the body known as Mnk kinase, which is thought to be involved in the development of a variety of cancers.

Key facts

Study ID

NCT03414450

Run by

EDDC (Experimental Drug Development Centre), A*STAR Research Entities

People needed

0

Starts

2018-04-25

Expected to finish

2023-02-01

Last updated by the study team

2018-10-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Each patient (male or female) must meet all of the following criteria to be enrolled in this study:
• Capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
• Age 18 years or older (US sites) or 21 years or older (Singapore site) at Baseline.
• Bone marrow (BM) cytogenetic analysis with at least 20 metaphase cells, confirmed advanced haematologic malignancies in any of the 4 following disease populations at Screening:
• CML-AP, Ph+
• CML-BC, Ph+
• Ph+ ALL
• Ph- ALL with relapsed and refractory disease who have exhausted all available therapy (for patients who develop T315I mutation related resistance, the definition requires failure of ponatinib treatment if drug is accessible).
• Meets definition for one of the following study subgroups:
• CML-AP:
• ≥ 15% and < 30% blast in peripheral blood or bone marrow, or
• ≥ 20% basophils in peripheral blood or bone marrow or
• ≥ 30% blasts + promyelocytes in peripheral blood or bone marrow (but < 30% blasts) or
• < 100 x 10\^9 platelets/L in peripheral blood unrelated to therapy or
• Cytogenetic, genetic evidence of clonal evolution and
• No extramedullary disease.
• CML-BC:
• ≥ 30% blasts in peripheral blood or bone marrow, or
• extramedullary disease other than hepatosplenomegaly.
• Ph+ ALL:
• ≥ 30% blasts in blood or bone marrow and
• no prior history of CML.
• Ph- ALL:
• ≥ 10% blasts in bone marrow.
• ECOG performance status of 0 to 2 at Baseline.

You may not qualify if…

• Patients meeting any of the following criteria will be excluded from the study:
• Is a male patient with sexual partner(s) of childbearing potential who is unwilling to use a highly effective method of contraception, one of which includes a condom. Sexually active male patients must use a condom during intercourse throughout the study and for 12 weeks after the end of treatment and should not father a child in this period. A condom is required to be used also by vasectomised males in order to prevent potential delivery of the study drug via seminal fluid. Female partners of male patients must be advised to also use one of the following contraception methods:
• intrauterine device or intrauterine system;
• prior sterilisation; or
• total abstinence from male/female intercourse.
• Is a female patient of childbearing potential, defined as a female physiologically capable of becoming pregnant (including a female whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, and females whose partners have been sterilised by vasectomy or other means), unless they are using a highly effective method for birth control throughout the study and for 12 weeks after the end of treatment. Highly effective methods for birth control include the following:
• Total abstinence: This is an acceptable method when this is consistent with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Female sterilisation: The patient has had a surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks prior to taking study drug. In case of an oophorectomy alone, the reproductive status of the patient must have been confirmed by follow-up hormone level assessment.
• Male partner sterilisation: The patient has the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. (For female patients on the study, the vasectomised male partner should be the sole partner for that patient.) These patients must also agree to the use an intrauterine device or intrauterine system AND a barrier method of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, or cream, or vaginal suppository. Reliable contraception must be maintained throughout the study and for 12 weeks after study drug discontinuation.
• Females considered post-menopausal and not of childbearing potential: The definition applies to females who have had 12 months of natural (spontaneous) amenorrhoea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhoea with serum follicle-stimulating hormone (FSH) levels > 40 million international units per milliliter (mIU/mL) (for US only: and estradiol < 20 pg/mL) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks prior to starting treatment. In the case of oophorectomy alone, only when the reproductive status of the patient has been confirmed by follow-up hormone level assessment is she considered not of childbearing potential.
• Is a pregnant or nursing (lactating) female, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
• Has dasatinib intolerance (haematologic and non-haematologic). Defined as: CTCAE Grade >2
• Has received anti-cancer therapy within 2 weeks or 5 half-lives, whichever is shorter (except for hydroxyurea, steroids, allopurinol, febuxostat, rasburicase, and intravenous hydration), prior to starting study drug or the side effects of such therapy have not resolved to Grade ≤1 within 2 weeks prior to starting study drug.
• Is receiving concomitant anti-cancer therapy (except for hydroxyurea, steroids, anagrelide, allopurinol, febuxostat, rasburicase, and intravenous hydration during the first week of the study drug[s] administration, or corticosteroids when appropriate).
• Has used other investigational drugs within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose of study drug.
• Has undergone autologous or allogenic stem cell transplantation < 60 days prior to the first dose of study drug;
• Has any evidence of on-going graft-versus-host disease (GVHD).
• Has evidence of another malignancy not in remission or history of such a malignancy within the last 3 years (except for treated basal or squamous cell carcinoma of the skin, or in situ cancer of the cervix).
• Has central nervous system (CNS) metastases.
• Has significant bleeding disorder unrelated to the disease.
• Has a history of long QT syndrome or prolonged QT interval corrected based on Fridericia's method (QTcF) > 450 ms.
• Has ECG evidence of complete left bundle branch block, or ventricular pacing.
• Has abnormalities in the 12-lead ECG that in the opinion of the Investigator increase the risk of participating in the study (e.g., sinus rhythm with PR interval > 240 ms or second degree or higher atrioventricular (AV) block confirmed by a repeat ECG).
• Has blood pressure and heart rate (HR) higher than 160/100 mmHg and 100 beats per minute (bpm), respectively, or lower than 80/50 mm Hg and 45 bpm, respectively, confirmed by a repeat assessment.
• Is receiving treatment with drugs known to be associated with Torsade de Pointes.

Where it is running

• Winship Cancer Institute, Emory University — Atlanta, Georgia, United States
• The Center for Cancer and Blood Disorders — Bethesda, Maryland, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Oregon Health & Science University — Portland, Oregon, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Singapore General Hospital — Singapore, Singapore

Full record on ClinicalTrials.gov

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