Trial Title:
Tulmimetostat (CPI-0209) in Patients With Mycosis Fungoides and Sézary Syndrome
NCT ID:
NCT05944562
Condition:
Mycosis Fungoides
Sezary Syndrome
Mycosis Fungoides/Sezary Syndrome
Conditions: Official terms:
Mycoses
Mycosis Fungoides
Sezary Syndrome
Syndrome
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tulmimetostat
Description:
Patients should take CPI-0209 at approximately the same time every morning in a fasted
state (no food for 2 hours prior and 1 hour following CPI-0209 dosing). Each dose of
CPI-0209 should be taken with a glass of water and consumed over as short a time as
possible.
Arm group label:
Dose De-Escalation Cohort: Tulmimetostat (CPI-0209)
Arm group label:
Dose Expansion Cohort: Tulmimetostat (CPI-0209)
Other name:
CPI-0209
Summary:
The hypotheses of this study are that single agent CPI-0209 will be safe and well
tolerated in patients with advanced (stage IB-IVB) mycosis fungoides (MF)/Sézary syndrome
(SS) who have had at least one prior systemic therapy, and that in these patients,
CPI-0209 will demonstrate efficacy and be worth of further study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed mycosis fungoides or Sézary syndrome,
stages IB to IVB with measurable disease and/or detectable blood involvement based
on the Global Response Criteria for CTCL (Olsen et al., 2022).
- Received at least one prior line of systemic therapy.
- At least 18 years of age.
- ECOG performance status ≤ 2
- Adequate counts and organ function as defined below:
- ANC ≥ 0.7 x 109/L, without growth factor support (filgrastim or pegfilgrastim)
for at least 14 days
- Platelets ≥ 75 x 109/L, without platelet transfusion for at least 14 days
- Hemoglobin ≥ 8.0 g/dL, with or without transfusion
- Serum total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
- Creatinine clearance > 30 mL/min by Cockcroft-Gault (using actual body weight)
for patients with creatinine levels above institutional normal OR serum
creatinine ≤ 1.5 x ULN
- Patients with treated brain metastases are eligible if follow-up brain imaging after
CNS-directed therapy shows no evidence of progression.
- The effects of CPI-0209 on the developing human fetus are unknown. For this reason,
women of childbearing potential and men must agree to use highly effective methods
of contraception for the duration of study participation and for 183 days after the
last dose of CPI-0209 for female patients and female partners of male patients, or
for 93 days after the last dose of CPI-0209 for male patients and male partners of
female patients. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed
consent document.
Exclusion Criteria:
- Prior treatment with an EZH2 inhibitor.
- Patients with CNS lymmphoma.
- A history of other malignancy with the exception of malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease. Patients with a prior or concurrent malignancy whose natural
history or treatment does not have the potential to interfere with the safety or
efficacy assessment of the investigational regimen are eligible for this trial.
- Those with local basal cell or squamous cell carcinoma of the skin, cervical
carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer
without known metastatic disease and with no requirement for therapy or
requiring only hormonal therapy and with normal prostate-specific antigen for ≥
1 year prior to registration, asymptomatic breast cancer on adjuvant hormonal
therapy diagnosed more than 2 years ago, adequately treated Stage 1 or 2 cancer
currently in complete remission, or any other cancer that has been in complete
remission for ≥ 3 years are eligible.
- Currently receiving any other investigational agents. Concomitant use of another
systemic therapy for MF/SS. Patients must have the following minimum wash-out from
previous treatments:
- At least 8 weeks for low-dose (12 Gy or less) total skin electron beam therapy
(TSEBT)
- At least 4 weeks for systemic cytotoxic anticancer agents or for
tumor-targeting monoclonal antibodies (mAbs), with the exception of
alemtuzumab, for which the washout is at least 16 weeks
- At least 2 weeks or 5 half-lives for systemic retinoids, interferons,
vorinostat, romidepsin, and denileukin diftitox, or anticancer investigational
agents that are not defined as immunotherapy,
- At least 2 weeks for local radiation therapy
- At least 1 week for topical retinoids, nitrogen mustard, or imiquimod
- Taking concomitant medication(s) or food or beverage that are strong CYP3A inducers
or inhibitors within 7 days prior to the first dose of study drug.
- History of allogeneic HCT within 90 days prior to the first dose of study drug.
- Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic
immunosuppressive prophylaxis or treatment.
- Previous solid organ transplant.
- Clinically significant cardiovascular disease including:
- Myocardial infarction/stroke within 3 months prior to Day 1 of treatment
- Unstable angina within 3 months prior to Day 1 of treatment
- Congestive heart failure or cardiomyopathy with NYHA Class 3 or 4
- History of clinically significant ventricular arrhythmias (e.g. ventricular
tachycardia, ventricular fibrillation, Torsades de pointes)
- Uncontrolled hypertension (as defined per institutional standards) despite 2
concomitant antihypertensive therapies
- QT interval corrected by the Fridericia correction formula (QTcF) ≥ 480 msec at
time of screening
- Major surgery within 4 weeks before starting study drug or not recovered from any
effects of prior major surgery (uncomplicated central line placement or fine needle
aspiration are not considered major surgery).
- Gastrointestinal disorders, i.e., ulcerative colitis, malabsorption syndrome,
refractory nausea and vomiting, biliary shunt, significant bowel resection or any
other condition that may significantly interfere with absorption of the study
medication by the investigator's assessment.
- Uncontrolled active infection requiring IV antibiotic, antiviral, or antifungal
medications within 14 days before the first dose of study drug. Infections (e.g.,
urinary tract infection) controlled on concurrent antimicrobial agents and
antimicrobial prophylaxis per institutional guidelines are acceptable.
- Current known active or chronic infection with HIV, hepatitis B, or hepatitis C. All
patients will require serologic testing to be performed within 6 months prior to
C1D1.
- Patients with chronic HBV or HCV are defined as patients with positive
hepatitis B serology: Patients with a negative HBsAg and a positive HBcAb
require an undetectable/negative hepatitis B DNA test (e.g. polymerase chain
reaction [PCR] test) to be enrolled, and will require prophylactic antiviral
treatment initiated prior to the first dose of study drug, and continued until
approximately 6 to 12 months after completion of study drug(s).
- Patients should be excluded if they have a condition requiring systemic treatment
with either corticosteroids (>10 mg daily prednisone equivalents) or other
immunosuppressive medications within 7 days of study drug administration. Inhaled or
topical steroids, steroids for physiologic or adrenal replacement doses <10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.
Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption) and use of these
agents does not require a washout period. A brief course of corticosteroids for
prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune
conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
is permitted. Topical steroids for cutaneous manifestations of MF/SS will be
permitted as per below:
- Continued use of select concomitant topical steroids is permitted if the
patient has remained clinically stable for at least 4 weeks. Patients who are
on low or moderate potency topical corticosteroids may participate if they are
on a stable dose for at least 4 weeks before enrollment. Local injections of
corticosteroids are acceptable; all corticosteroids will be reported as
concomitant medications. Patients prescribed prednisone 10 mg PO daily or less
(or equivalent) will not be excluded.
- Ongoing treatment with other immunosuppressive agent including, but not limited to,
methotrexate, azathioprine, anti-TNF agents, etc. with the exception of steroids.
- Clinically active or symptomatic chronic liver disease.
- Unstable or severe uncontrolled medical condition or any important medical or
psychiatric illness or abnormal laboratory finding that would, in the investigator's
judgment, increase the risk to the patient associated with his/her participation in
this study.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 72 hours prior to first dose of study drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Neha Mehta-Shah, M.D.
Phone:
314-747-7510
Email:
mehta-n@wustl.edu
Investigator:
Last name:
Neha Mehta-Shah, M.D.
Email:
Principal Investigator
Investigator:
Last name:
Nicole C Foley, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Amy Musiek, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Jacqueline Payton, M.D., Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
George Souroullas, Ph.D.
Email:
Sub-Investigator
Investigator:
Last name:
Fei Wan, Ph.D.
Email:
Sub-Investigator
Start date:
January 9, 2024
Completion date:
January 31, 2030
Lead sponsor:
Agency:
Washington University School of Medicine
Agency class:
Other
Collaborator:
Agency:
MorphoSys AG
Agency class:
Industry
Collaborator:
Agency:
The Foundation for Barnes-Jewish Hospital
Agency class:
Other
Collaborator:
Agency:
Swim Across America
Agency class:
Other
Collaborator:
Agency:
Daniel E. Corbin Jr. Lymphoma Fund
Agency class:
Other
Source:
Washington University School of Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05944562
http://www.siteman.wustl.edu
