Cobimetinib in Newly Diagnosed or HMA-treated CMML Patients With RAS Pathway Mutations (CONCERTO)

  • STATUS
    Recruiting
  • End date
    Aug 15, 2026
  • participants needed
    29
  • sponsor
    University of Utah
Send
Updated on 12 April 2023
See if I qualify

Summary

This is an open-label, nonrandomized phase 2 trial to assess the efficacy of cobimetinib in RAS pathway activated CMML.

All eligible patients will be treated daily with cobimetinib in 28-day cycles. Cobimetinib will be administered for three weeks followed by a one week break prior to the start of the following cycle. Patients will remain on study therapy until treatment discontinuation criteria is met.

Description

This is an open-label, nonrandomized phase 2 trial to assess the efficacy of cobimetinib in RAS pathway activated CMML. Two cohorts of patients will be accrued using Simon's two-stage design (Simon, 1989) for both cohorts. Cohort 1 will enroll nine newly diagnosed patients in the first stage and if four or more responses are observed five additional patients will be enrolled in the second stage. Cohort 2 will enroll six HMA refractory patients in the first stage and if one or more responses are observed then nine additional patients will be enrolled in the second stage.

All eligible patients will be treated daily with cobimetinib in 28-day cycles. Cobimetinib will be administered consecutively for three weeks followed by a one week break prior to the start of the following cycle. Patients will remain on study therapy until treatment discontinuation criteria is met.

Details
Condition Chronic Myelomonocytic Leukemia (CMML)
Treatment Cobimetinib
Clinical Study IdentifierNCT04409639
SponsorUniversity of Utah
Last Modified on12 April 2023

Eligibility

 Yes No Not Sure

Inclusion Criteria

Male or female subject aged ≥ 18 years
Newly diagnosed or hypomethylating agent (HMA) refractory chronic myelomonocytic leukemia (CMML -0/-1/-2; 2016 WHO classification) with RAS pathway activation as determined by standard of care hematopoietic cell sequencing results on peripheral blood or bone marrow demonstrating NRAS, KRAS, PTPN11, FLT3, CBL, JAK2, BRAF or NF1 mutations at variant allele frequency ≥ 5%. BMBx, NGS, FISH, and cytogenetics should be done at the primary trial site within 21 days prior to C1D1. The FLT3-ITD PCR allelic ration must be ≥ 0.05 on testing done on screening biopsy (NOTE: cannot quantitate FLT3-ITD VAF by NGS, must be a separate PCR test)
ECOG Performance Status ≤ 3
Adequate organ function as defined as
Hepatic
Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
Unless elevation is related to Gilbert's syndrome, hemolysis, or thought to be due to leukemic hepatic involvement
AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Unless elevation is related to leukemic hepatic involvement
Renal
\---Serum creatinine ≤ 2x ULN
OR
Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula
Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)
Females: (((140-age)×weight[kg])/(serum creatinine [mg/dL]×72))×0.85
Left ventricular function ≥ 50% as assessed by echocardiogram
Negative pregnancy test for women of childbearing potential or evidence of post-menopausal status. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply
Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
Highly effective contraception for both male and female subjects throughout the study
and at least 3 months after the last dose of study therapy as described in
Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
Section 7.4 of the protocol
Recovery to baseline or Grade ≤ 1 CTCAE v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy

Exclusion Criteria

Previous exposure to experimental MEK inhibitors for CMML
Grade 2 or greater QTc prolongation on screening electrocardiogram (ECG) or clinically significant cardiovascular disease (uncontrolled or symptomatic atrial arrhythmias, congestive heart failure, myocardial infarction/CABG/PCI within 6 months of screening, uncontrolled arterial hypertension or history of ventricular arrhythmia)
Clinical or laboratory evidence of central nervous system (CNS) leukemia
Major surgery within 4 weeks prior to study drug initiation
History of interstitial lung disease
History of retinal detachment, central serous retinopathy (CSR), retinal vein occlusion (RVO), or at high risk for CSR or RVO following screening ophthalmologic exam at discretion of PI/Sub-I following review of exam findings, and, if necessary, consultation with ophthalmology provider
Patients with muscular and/or neuromuscular disorders associated with elevated CPK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, or spinal muscular atrophy)
Any active significant gastrointestinal dysfunction as determined by the clinical investigator to interfere with the patient's ability to swallow or absorb the study treatment, (i.e. refractory nausea and vomiting, malabsorption and external biliary shunt)
Pregnant or nursing (lactating) women
On chronic treatment with strong CYP3A inhibitors or patients taking St. John's Wort, carbamazepine, efavirenz, phenytoin, rifampin, and other strong and moderate CYP3A inducers
Known HIV infection with a detectable viral load at the time of screening
\--Note: Patients on effective antiretroviral therapy with an undetectable
Diagnosis of any other malignancy within 2 years before study enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or cervix, low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (eg, surgery, radiation, or castration), or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms, or any solid tumor malignancy that has been adequately treated for which there is no evidence of disease. Patients with monoclonal gammopathy of undetermined significance (MGUS) are permitted to enroll
viral load at the time of screening are eligible for this trial
Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or hepatitis C
\--Note: Patients with a past or resolved HBV infection (defined as the
presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Patients positive for hepatitis C (HCV) antibody are eligible only
if polymerase chain reaction is negative for HCV RNA
Subjects taking prohibited medications as described in Section 6.3.2. A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur before the start of treatment
Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study
Known prior severe hypersensitivity to cobimetinib or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3)
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name
Edit Delete

Added by • 

 • 

Private

Edit Delete

Reply by • • Private
Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note