Thrombocythemia, Essential
Conditions
Brief summary
This is a single-center, open-label investigator-initiated trial evaluating the effects of IMG-7289 administered orally once daily in patients with essential thrombocythemia.
Interventions
DRUGIMG-7289
Single starting dose with individualized dose titrations throughout
Sponsors
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Diagnosis of Essential Thrombocythemia per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al., 2016). * 3\. Patients who are intolerant or resistant to hydroxyurea per ELN (European Leukemia Net) criteria, or in the Investigator's judgment are not candidates for available approved therapy. The ELN definitions of resistance/intolerance to HU (hydroxyurea) requires the fulfillment of at least one of the following criteria: * Platelet count greater than 600 × 109/L after 3 months of at least 2 g/day of HU (2.5 g/day in patients with a body weight over 80 kg); * Platelet count greater than 400 × 109/L and leukocytes less than 2.5 × 109/L or hemoglobin (Hb) less than 100 g/L at any dose of HU; * Presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of HU; * HU-related fever. * Requires treatment in order to lower platelet counts based on the Clinically Relevant IPSET (International Prognostic Score for Thrombosis in Essential Thrombocythemia) -Thrombosis Guidelines. * Platelet count \>450 x 109/L pre-dose Day 1. * Peripheral blast count \<10% pre-dose Day 1. * ANC (absolute neutrophil count) ≥0.5 x 109/L pre-dose Day 1. * Fibrosis Score ≤ grade 2, as per a slightly modified version (Arber et al., 2016) of the European Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005). * Life expectancy \> 36 weeks. * Able to swallow capsules. * Amenable to spleen size determination, bone marrow evaluations, and peripheral blood sampling during the study. * Must have discontinued ET therapy at least 2 weeks (4 weeks for interferon) prior to study drug initiation. * Agrees to use an approved method of contraception from Screening until 28 days after last administration of the study drug. Acceptable methods of birth control include: birth control pills, depo-progesterone injections, a vaginal hormonal contraceptive ring, a barrier contraceptive such as a condom with spermicide cream or gel, diaphragms or cervical cap with spermicide cream or gel, or an intrauterine device (IUD). * If male, agrees not to donate sperm or father a child for at least one month after the last dose of the study medication.
Exclusion criteria
* Greater than 3 separate transfusion episodes over the last 6 months and/or any transfusion over the last 4 weeks. * Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater. * Currently pregnant or planning on being pregnant in the following 6 months or currently breastfeeding. * Currently residing outside the United States. * History of splenectomy. * Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1). * Uncontrolled active infection. * Known positive for HIV or infectious hepatitis, type A, B or C. * Current use of monoamine oxidase A and B inhibitors (MAOIs). * Evidence at the time of screening of increased risk of bleeding, including any of the following: 1. Activated partial thromboplastin time (aPTT) \> 1.3 x the upper limit of normal 2. International normalized ratio (INR) \>1.3 x the local upper limit of normal 3. Known Acquired Von Willebrand's disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Patients Who Achieve Complete Hematologic Remission at Week 24 Using ELN Response Criteria for ET (Barosi et al., 2013) | 24 weeks | ELN criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Additional Therapy Period (ATP) Overall Symptom Burden | 24 weeks to 48 weeks (may repeat) | Symptom Forms will be completed by participants each week of participation in the study- even on weeks with no study visit. Symptom Form are completed at around the same time on each of the following days: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85, Day 92, Day 99, Day 106, Day 113, Day 120, Day 127, Day 134, Day 141, Day 148, Day 155, Day 162 and Day 169. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IMG-7289 IMG-7289: Single starting dose with individualized dose titrations throughout | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | IMG-7289 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
The Proportion of Patients Who Achieve Complete Hematologic Remission at Week 24 Using ELN Response Criteria for ET (Barosi et al., 2013)
ELN criteria
Time frame: 24 weeks
Population: Only 4 of the 5 completers were evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMG-7289 | The Proportion of Patients Who Achieve Complete Hematologic Remission at Week 24 Using ELN Response Criteria for ET (Barosi et al., 2013) | 0 Percentage of Participants |
Secondary
Additional Therapy Period (ATP) Overall Symptom Burden
Symptom Forms will be completed by participants each week of participation in the study- even on weeks with no study visit. Symptom Form are completed at around the same time on each of the following days: Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, Day 43, Day 50, Day 57, Day 64, Day 71, Day 78, Day 85, Day 92, Day 99, Day 106, Day 113, Day 120, Day 127, Day 134, Day 141, Day 148, Day 155, Day 162 and Day 169.
Time frame: 24 weeks to 48 weeks (may repeat)