Trial Title:
A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) Who Have Been Failed by a Type I JAK2 Inhibitor (JAK2i)
NCT ID:
NCT06343805
Condition:
Primary Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
PMF
PPV-MF
PET-MF
Conditions: Official terms:
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This dose escalation study will follow a 3+3 cohort design until the RP2D and/or MTD is
determined.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AJ1-11095
Description:
Type II JAK2 Inhibitor
Arm group label:
Cohort 1
Arm group label:
Cohort 2
Arm group label:
Cohort 3
Arm group label:
Cohort 4
Arm group label:
Cohort 5
Arm group label:
Dose Expansion Cohort 1
Arm group label:
Dose Expansion Cohort 2
Summary:
AJX-101 is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label
clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK),
clinical activity and changes in biomarkers of an orally administered type II JAK2
inhibitor, AJ1-11095, in subjects with primary or secondary myelofibrosis previously
treated with at least one type I JAK2 inhibitor.
Detailed description:
This is a phase 1, non-randomized, open-label study utilizing a 3+3 sequential dose
escalation design followed by an expansion phase. The primary objective will be to
evaluate the safety and tolerability of AJ1-11095, and establish a Maximally Tolerated
Dose (MTD) and/or inform the establishment of a candidate Recommended Phase 2 dose
(RP2D). The RP2D may be the maximally tolerated dose (MTD) or may be a dose below the
MTD. The candidate RP2D will be based on AE pattern, PK and biomarker information, in
addition to all available safety and efficacy data. Expansion cohorts will be enrolled to
gather additional safety and efficacy information and to further refine input for future
RP2D discussions. Eligible participants will have PMF, PPV-MF or PET-MF and will have
either have relapsed after a response, or be refractory to, at least one prior type I
JAK2 inhibitor therapy, either administered as monotherapy or in combination with another
drug.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 18 years of age or older.
2. Diagnosis of PMF, post-PV MF, or post-ET MF.
3. DIPSS Intermediate-2 or High-risk MF with ≤10% blasts, regardless of JAK2 mutation
status.
4. Estimated spleen volume ≥450cm3.
5. MFSAF v.4.0 TSS ≥10, or at least 2 of 7 MFSAF-assessed symptoms with scores ≥3.
6. ECOG PS of 0, 1, 2, or 3.
7. Prior therapy with at least 1 type I JAK2 inhibitor, and either failed to achieve a
response or relapsed after achieving a response.
8. ANC ≥1.0×10^9/L.
9. Platelet count ≥75×10^9/L.
10. eGFR ≥45 mL/min/1.73m2.
11. Serum total bilirubin ≤2.0 × upper limit of normal (ULN).
12. AST and ALT ≤3.0 × ULN.
13. QTcF ≤480 msec.
Exclusion Criteria:
1. Prior splenectomy.
2. Splenic irradiation within 3 months prior to first dose of study drug.
3. Ongoing use of systemic corticosteroids at dose equivalent to >10mg/day of
prednisone.
4. Uncontrolled intercurrent illness such as an acute infection.
5. Chronic active or acute hepatitis B or C infection.
6. Chemotherapy in the previous 4 weeks prior to first dose of study drug (Hydrea is
permitted until 5 days before starting protocol therapy).
7. Use of a JAK2 inhibitor in the previous 10 days.
8. Use of erythropoiesis stimulating agents (unless stable for >8 weeks).
9. Peripheral neuropathy ≥ Grade 2 (NCI CTCAE v 5.0).
10. Unable or unwilling to undergo CT or MRI for spleen size imaging.
11. Pregnant or breastfeeding.
12. Requirement for therapy with a medication that is a strong CYP3A4 inhibitor as a
concomitant medication.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Andrew Kuykendall, MD
Phone:
813-745-4639
Facility:
Name:
University of Kansas Medical Center
Address:
City:
Kansas City
Zip:
66160
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Abdulraheem Yacoub, MD
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Gabriela Hobbs, MD
Phone:
617-724-1124
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jacqueline Garcia, MD
Phone:
617-632-1906
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Stephen Oh, MD
Phone:
314-362-8814
Facility:
Name:
David H. Koch Center for Cancer Care at Memorial Sloan Kettering
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Raajit Rampal
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Contact:
Last name:
John Mascarenhas, MD
Phone:
212-241-8839
Email:
mikaela.dougherty@mssm.edu
Contact backup:
Last name:
Mikaela Dougherty
Facility:
Name:
Levine Cancer Institute
Address:
City:
Charlotte
Zip:
28204
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Michael Grunwald, MD
Phone:
980-442-4363
Facility:
Name:
University of Cincinnati
Address:
City:
Cincinnati
Zip:
45221
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
John Byrd
Phone:
614-620-6533
Facility:
Name:
The Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Uma Borate, MD
Phone:
614-685-9828
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Prithviraj Bose, MD
Phone:
713-792-7747
Start date:
October 2024
Completion date:
February 15, 2027
Lead sponsor:
Agency:
Ajax Therapeutics, Inc.
Agency class:
Industry
Source:
Ajax Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06343805
