Trial Title:
Open Label Phase 2 Study of Tasquinimod in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)
NCT ID:
NCT06327100
Condition:
Primary Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Post-Essential Thrombocytosis Myelofibrosis
Conditions: Official terms:
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ruxolitinib
Description:
Given by PO
Arm group label:
Group 2
Other name:
Jakafi
Other name:
INCB018424
Other name:
INC424
Intervention type:
Drug
Intervention name:
Tasquinimod
Description:
Given by PO
Arm group label:
Group 1
Arm group label:
Group 2
Summary:
To learn if tasquinimod either alone or in combination with ruxolitinib can help to
control PMF, post-PV MF, or post-ET MF.
Detailed description:
Primary Objectives To determine anti-tumor activity of tasquinimod in patients with PMF,
post-PV MF, and post-ET MF in a monotherapy and in combination with stable dose of
ruxolitinib based on the measurement of the objective response rate (ORR) which is
defined as the proportion of patients with CR (complete remission), PR (partial
remission), or CI (clinical improvement) after six cycles of treatment, according to the
International Working Group (IWG) consensus criteria.
Secondary Objectives To determine safety of tasquinimod in patients with PMF, post-PV MF,
and post-ET MF in a monotherapy and in combination with stable dose of ruxolitinib
To determine time to response and response duration.
To assess changes in symptom burden as assessed by Myeloproliferative Neoplasm Symptom
Assessment Form Total Symptom Score (MFSAF v4.0).
To assess changes in bone marrow fibrosis grade.
To assess the pharmacokinetics (PK) of tasquinimod in blood to determine whether the
systemic exposure of tasquinimod, when administered alone or in combination with
ruxolitinib in patients with MF.
To assess correlation of response / resistance to tasquinimod with baseline genetic
markers (cytogenetic alterations and mutations determined by NextGen sequencing of an
81-gene myeloid panel).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Participants eligible for inclusion in this study have to meet the following criteria:
Myelofibrosis MF Monotherapy:
Participants who are not candidates for, intolerant of, or relapsed/refractory to
approved JAKi (ruxolitinib and / or fedratinib / pacritinib) or when further benefit from
therapy is not anticipated per investigator. Participants not eligible for JAKi therapy
irrespectively of previous treatments. Prior JAKi therapy is not required.
Myelofibrosis Ruxolitinib Combination MF participants treated with Ruxolitinib for at
least 3 months on a stable, uninterrupted dose for at least 2 months prior to study
enrollment AND have suboptimal response (palpable spleen of ≥5 cm, or total symptoms
score of ≥10) or progressive anemia/thrombocytopenia/neutropenia.
AND all the below criteria in both cohorts:
- Must be diagnosed with treatment requiring PMF or post ET/PV MF diagnosed according
to the 2016 World Health Organization with intermediate -1, intermediate -2 or
high-risk disease according to the DIPSS prognostic scoring system, or if with low
risk disease then with symptomatic splenomegaly that is ≥ 5 cm below left costal
margin by physical exam.
- Peripheral or bone marrow blasts must be < 10%
- Participants must provide written informed consent.
- Age 18 years or older. Because no dosing or adverse event data are currently
available on the use of tasquinimod as monotherapy or in combination with
ruxolitinib in patients <18 years of age, children are excluded from this study.
- Willing and able to comply with scheduled visits, treatment plan and laboratory
tests.
- Participant is able to swallow and retain oral medication.
- ECOG performance status 0-2.
- Required baseline laboratory status:
- Absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/mm3)
- Serum direct bilirubin ≤ 1.0 x ULN (upper limit of normal)
- AST (SGOT) or ALT (SGPT) [if both measured, then this applies to both
measurements] ≤ 2.5 x ULN, except for participants with MF involvement of the
liver who must have levels ≤ 5 x ULN
- Glomerular Filtration Rate (GFR) of ≥ 30 ml/min based on Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation using serum or plasma creatinine
or cystatin-C.
- Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1.
- At least 2 weeks from prior investigational MF-directed treatment (till the start of
study drug). This excludes concurrent ruxolitinib which is allowed in combination
cohort. Hydroxyurea is allowed as standard cytoreductive therapy up until one day
prior to initiation of therapy with tasquinimod. No other standard of care therapy
for MF is allowed (as specified in the exclusion criteria)
- For women of childbearing potential, a documented negative serum or urine pregnancy
test within 14 days prior to the administration of study drug.
- The effects of tasquinimod on the developing human fetus are unknown. For this
reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation. (Refer to Pregnancy
Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all
female participants, between the onset of menses (as early as 8 years of age) and 55
years unless the patient presents with an applicable exclusionary factor which may
be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal
range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization
procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e. birth
control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine
device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy,
Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging
in sexual activity for the total duration of the trial and the drug washout period
is an acceptable practice; however periodic abstinence, the rhythm method, and the
withdrawal method are not acceptable methods of birth control. Should a woman become
pregnant or suspect she is pregnant while she or her partner is participating in
this study, she should inform her treating physician immediately.
- Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 6
months after completion of tasquinimod administration.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
Participants eligible for this study must not meet any of the following criteria:
- Any concurrent severe and/or uncontrolled medical conditions that could increase the
participant's risk for toxicity while in the study or that could confound
discrimination between disease- and study treatment-related toxicities.
- Impaired cardiac function or clinically significant cardiac diseases, including any
of the following:
- History or presence of ventricular tachyarrhythmia.
- Presence of unstable atrial fibrillation (ventricular response > 100 bpm);
Participants with stable atrial fibrillation are eligible, provided they do not
meet any of the other cardiac exclusion criteria.
- Clinically significant resting bradycardia (< 50 bpm).
- Angina pectoris or acute myocardial infarction ≤ 3 months prior to starting
study drug.
- Other clinically significant heart disease (e.g., symptomatic congestive heart
failure; uncontrolled arrhythmia or hypertension; history of labile
hypertension or poor compliance with an antihypertensive regimen).
- Participants who are currently receiving chronic (> 14 days) treatment with
corticosteroids at a dose ≥ 10 mg of prednisone (or its glucocorticoid equivalent)
per day, or any other chronic immunosuppressive treatment that cannot be
discontinued prior to starting study drug.
- Treatment with chemotherapy (except hydroxyurea within 1 day prior to study
treatment), immunomodulatory drug therapy (e.g. thalidomide, interferon-alpha),
platelet-reducing therapy (e.g. anagrelide), immunosuppressive therapy, and
erythropoetin use within 28 days prior to study treatment
- Treatment with experimental therapy within the past 2 weeks or 5 half-lives,
whichever is shorter
- Treatment with tasquinimod at any time
- Participants with impairment of gastrointestinal (GI) function or GI disease that
may significantly alter the absorption of tasquinimod as per physician opinion
- Participants with known or active (acute and chronic) Hepatitis A, B, or C; and
Hepatitis B and C carriers, HIV. Participants are excluded regardless of
detectability of viral load (lack of safety data).
- Participants with clinically significant bacterial, fungal, parasitic or viral
infection which require therapy
- History of pancreatitis
- History of malabsorption or other condition that would interfere with absorption of
study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome, small bowel resection)
- Systemic treatment within 14 days prior to the initiation of study treatment with
any of the following moderate or strong inhibitor, or moderate or strong inducer of
cytochrome P-3A4 (CYP3A4): imidazoles (e.g. ketoconazole), protease inhibitors (e.g.
ritonavir), macrolides (e.g. erythromycin), rifampicin, rifabutin, phenytoin,
carbamazepine, St. John's wort.
- Need for ongoing therapy with any of the following drug substances of narrow
therapeutic range that are metabolized mainly by CYP3A4: alfentanil, fentanyl,
quinidine, astemizole, terfenadine, sirolimus, tacrolimus, cyclosporine, cisapride,
and ergotamine
- Need for ongoing therapy with any of the following drug substances of narrow
therapeutic range metabolized mainly by CYP1A2: duloxetine, palonosetron,
theophylline, tizanidine, and ondansetron.
- Need for ongoing therapy with any of the following drug substances of narrow
therapeutic range metabolized mainly by CYP2D6: Dosulepin, Flecainide, Sotalol,
Pimozide, Procainamide, Clonidine, Desipramine, Clomipramine, Amitriptyline,
Imipramine, Nortriptyline, Trimipramine, Amoxapine, Dronedarone, Phenytoin
- Ongoing treatment with warfarin, unless the INR is <=3.0.
- Known hypersensitivity to tasquinimod or any excipients in the study treatments
- Any other condition that would, in the Investigator's judgment, contraindicate
subject's participation in the clinical study due to safety concerns or compliance
with clinical study procedures
- Prior inclusion in this study
- Pregnant women are excluded from this study because tasquinimod is an agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with tasquinimod, breastfeeding should be discontinued if the mother is
treated with tasquinimod. These potential risks may also apply to other agents used
in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lucia Masarova, MD
Phone:
832-750-4211
Email:
lmasarova@mdanderson.org
Investigator:
Last name:
Lucia Masarova, MD
Email:
Principal Investigator
Start date:
August 1, 2024
Completion date:
May 1, 2031
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Active Biotech AB
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06327100
http://www.mdanderson.org
