Trial Title:
Onvansertib for the Treatment of Recurrent or Refractory Chronic Myelomonocytic Leukemia
NCT ID:
NCT05549661
Condition:
Recurrent Chronic Myelomonocytic Leukemia
Refractory Chronic Myelomonocytic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Onvansertib
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (onvansertib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration and Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (onvansertib)
Intervention type:
Drug
Intervention name:
Onvansertib
Description:
Given PO
Arm group label:
Treatment (onvansertib)
Other name:
'PLK1 Inhibitor PCM-075
Other name:
NMS-1286937
Other name:
PCM 075
Other name:
PCM-075
Other name:
PLK-1 Inhibitor PCM-075
Other name:
Polo-like Kinase 1 Inhibitor NMS-1286937
Other name:
Polo-like Kinase 1 Inhibitor PCM-075
Intervention type:
Procedure
Intervention name:
Ultrasound Imaging
Description:
Undergo ultrasound imaging
Arm group label:
Treatment (onvansertib)
Other name:
2-Dimensional Grayscale Ultrasound Imaging
Other name:
2-Dimensional Ultrasound Imaging
Other name:
2D-US
Other name:
Ultrasonography
Other name:
Ultrasound
Other name:
Ultrasound Test
Other name:
Ultrasound, Medical
Other name:
US
Summary:
This phase I trial evaluates the safety, effectiveness, and best dose of onvansertib for
the treatment of patients with chronic myelomonocytic leukemia that has come back
(recurrent) or that does not respond to treatment (refractory). Onvansertib is a drug
that binds to and inhibits an enzyme called PLK1, preventing cancer cell proliferation
and causing cell death.
Detailed description:
PRIMARY OBJECTIVE:
I. Characterization of adverse events (AEs) by type, incidence, severity (graded by
National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]
version 5.0), seriousness, and relationship to treatment; effects on vital signs and
laboratory parameters; changes from baseline in electrocardiograms (ECGs), physical
examinations, weight, and Eastern Cooperative Oncology Group (ECOG) performance status.
SECONDARY OBJECTIVES:
I. Efficacy: complete response (CR) rate, according to the 2015 myelodysplastic syndrome
(MDS)/myeloproliferative neoplasm (MPN) International Working Group (IWG) criteria.
II. Overall remission rate (ORR), defined as CR + complete cytogenetic remission +
partial remission (CR+ complete cytogenetic remission [CCR] + partial remission [PR]).
III. Volumetric spleen response rate, as determined by ultrasound scan (US). IV.
Constitutional symptoms, as assessed by the MPN-Symptom Assessment Form (SAF) total
symptom score (TSS).
EXPLORATORY OBJECTIVES:
I. Onvansertib activity in RAS mutant subtypes of proliferative chronic myelomonocytic
leukemia (CMML).
II. Monocyte subset analysis by flow cytometry (CD14/CD16). III. Relation of genomic
backgrounds and changes, as assessed by next generation sequencing (NGS), to response.
IV. Relation between changes in mutant circulating-tumor deoxyribonucleic acid (ctDNA)
and response.
V. CR rate, ORR and spleen response rate as per the 2015 MDS/MPN IWG response criteria.
VI. Assessment of target engagement. VII. Expression levels of PLK1 and KMT2A.
OUTLINE: This is a dose-escalation study of onvansertib followed by a dose-expansion
study.
Patients receive onvansertib orally (PO) once daily (QD) on study. Patients also undergo
bone marrow aspiration and biopsy, collection of blood samples, and ultrasound imaging
during screening and throughout the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- PRE-REGISTRATION - INCLUSION CRITERIA:
- Age >= 18 years
- Histological confirmation of World Health Organization (WHO)-defined diagnosis of
proliferative chronic myelomonocytic leukemia (CMML) (white blood cell (WBC) count
>= 13,000/mm^3)
- Relapsed/refractory following treatment with hydroxyurea; or at least 4 cycles of
treatment with hypomethylating agents; or who are intolerant of treatment with
either therapy. Note: Prior exposure to erythropoiesis stimulating agents is
allowed. Hydroxyurea may continue for the first 28 days on study. Continuation of
hydroxyurea beyond the first cycle must be discussed with the principal investigator
(PI)
- Willing and able to review, understand, and provide written consent before starting
any study-specific procedures or therapy
- Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)
- Willingness to provide mandatory bone marrow specimens for correlative research
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Recovered to grade 1 or baseline or established as sequelae from all toxic effects
of previous therapy except alopecia
- Platelet count >= 20,000/mm^3 (obtained =< 14 days prior to pre-registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (=< 3 x ULN for patients with
Gilbert's syndrome) (obtained =< 14 days prior to pre-registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained
=< 14 days prior to pre-registration)
- Estimated glomerular filtration rate (eGFR) >= 60 mL/min/m^2 using the
Cockcroft-Gault formula (obtained =< 14 days prior to pre-registration)
- Ability to complete questionnaire(s) by themselves or with assistance
- Willingness to provide mandatory blood specimens for correlative research
- REGISTRATION - INCLUSION CRITERIA:
- Histological confirmation of World Health Organization (WHO)-defined diagnosis of
proliferative CMML (WBC count >= 13,000/mm^3). NOTE: To confirm patient is still
eligible
- For a man or a woman of child-bearing potential (WOCBP): Must agree to use
contraception or take measures to avoid pregnancy during the study and for 180 days
after the final dose of any study drug. Adequate contraception is defined as
follows:
- Complete true abstinence
- Consistent and correct use of one of the following methods of birth control:
- Male partner who is sterile prior to the female patient's entry into the
study and is the sole sexual partner for that female patient
- Implants of levonorgestrel
- Injectable progestogen
- Intrauterine device (IUD) with a documented failure rate of less than 1%
per year
- Oral contraceptive pill (either combined or progesterone only)
- Barrier method, for example: diaphragm with spermicide or condom with
spermicide in combination with either implants of levonorgestrel or
injectable progestogen
- WOCBP must have a negative serum or urine pregnancy test =< 7 days prior to
registration
- NOTE: WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal
ligation, or bilateral oophorectomy) or is not postmenopausal (defined as
amenorrhea > 12 consecutive months); or women on hormone replacement therapy
with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL.
Even women who are using oral, implanted or injectable contraceptive hormones
or mechanical products such as an IUD or barrier methods (diaphragm, condoms,
spermicides) to prevent pregnancy or practicing abstinence or where partner is
sterile (eg, vasectomy), must be considered to be of child-bearing potential
- NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
Exclusion Criteria:
- PRE-REGISTRATION - EXCLUSION CRITERIA:
- Previous exposure to an alternative (investigational) PLK1 inhibitor
- MDS/MPN overlap syndromes other than CMML
- Prior allogeneic hematopoietic stem cell transplantation
- Active central nervous system disease
- Concurrent active malignancy, except adequately treated nonmelanoma skin cancer.
History of curatively treated in situ cancer of the cervix, curatively treated in
situ cancer of the breast, or other solid tumors curatively treated is allowed as
long as there is no evidence of disease for > 2 years
- New York Heart Association (NYHA) class III/IV heart failure or active angina/angina
equivalents
- Anticancer chemotherapy or biologic therapy administered within 2 weeks (and at
least 4 elimination half-lives for clinical trial agents) prior to pre-registration.
NOTE: Hydroxyurea is allowed for the first 28 days on study. Continuation of
hydroxyurea beyond the first cycle must be discussed with the PI
- Receiving any other investigational agent which would be considered as a treatment
for the primary neoplasm
- Major surgery =< 6 weeks prior to pre-registration
- Gastrointestinal (GI) disorder(s) that, in the opinion of the Investigator, would
significantly impede the absorption of an oral agent (eg, intestinal occlusion,
active Crohn's disease, ulcerative colitis, extensive gastric and small intestine
resection)
- Unable or unwilling to swallow study drug
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, clinically significant nonhealing or healing wounds, clinically
significant cardiac arrhythmia, significant pulmonary disease (shortness of breath
at rest or mild exertion), uncontrolled infection, or psychiatric illness/social
situations that would limit compliance with study requirements
- Known active infection with human immunodeficiency virus (HIV) with measurable viral
titer, hepatitis B surface antigen positivity, or hepatitis C with measurable viral
titer. NOTE: Patients with antibody to hepatitis B core antibody are eligible if
they have no measurable viral titer. Patients who have had a hepatitis B virus (HBV)
immunization are eligible
- Patient is receiving any live vaccine (eg, varicella, pneumococcus) =< 28 days prior
to pre-registration. NOTE: messenger ribonucleic acid (mRNA)-based (eg, Pfizer or
Moderna) or replication-deficient virus (eg, Oxford/AstraZeneca) COVID19 vaccines
are permitted
- Disease requiring systemic treatment with systemic immunosuppression with steroid
steroids at a dose of >= 20 mg/day prednisone (or equivalent). Exceptions:
Intermittent use of bronchodilators or inhaled steroids, local steroid injections,
topical steroids
- Any active disease condition that would render the protocol treatment dangerous or
impair the ability of the patient to receive study drug
- Strong CYP3A4 inhibitors/inducers as identified per institutional guidelines
- QT interval with Fridericia's correction (QTcF) > 470 milliseconds. In the case of
potentially correctible causes of QT prolongation, (eg, medications, hypokalemia),
the electrocardiogram (ECG) may be repeated once during screening and that result
may be used to determine eligibility
- REGISTRATION - EXCLUSION CRITERIA:
- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:
- Pregnant persons
- Nursing persons
- Persons of childbearing potential who are unwilling to employ adequate
contraception
- Increased risk of Torsade des Pointes (TdP) defined as follows:
- A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration
of a QTc interval > 480 msec [CTCAE Grade >= 2] using Fredericia's QT
correction formula)
- A history of additional risk factors for TdP (eg. heart failure, family history
of long QT syndrome)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trial Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Mrinal S. Patnaik, M.D.
Email:
Principal Investigator
Start date:
April 4, 2023
Completion date:
March 8, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05549661
https://www.mayo.edu/research/clinical-trials
