Brief Summary
To assess the safety and tolerability of CK0804 as add-on therapy in participants with myelofibrosis, with suboptimal response to ruxolitinib
Brief Title
Leading in MPNs Beyond Ruxolitinib in Combo With T-Regs
Detailed Description
1. Safety Run-in
The study will employ a 3+3+3 design to assess the safety and tolerability of the treatment based on treatment-limiting toxicities (TLTs) occurring up to 1 Cycle (28 days) after the first infusion.
2. Expansion
After a total of 9 participants completed 28 days and are evaluated for tolerability in the safety run-in phase, additional participants may be included in the expansion cohort in order to have approximately 24 evaluable myelofibrosis
The study will employ a 3+3+3 design to assess the safety and tolerability of the treatment based on treatment-limiting toxicities (TLTs) occurring up to 1 Cycle (28 days) after the first infusion.
2. Expansion
After a total of 9 participants completed 28 days and are evaluated for tolerability in the safety run-in phase, additional participants may be included in the expansion cohort in order to have approximately 24 evaluable myelofibrosis
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
713-806-4787
Central Contact Email
tara.sadeghi@cellenkosinc.com
Central Contact Role
Contact
Central Contact Phone
832-962-7628
Central Contact Email
stacy.minor@cellenkosinc.com
Completion Date
Completion Date Type
Estimated
Conditions
Myelofibrosis
Eligibility Criteria
Inclusion Criteria:
1. Ability to comprehend and willingness to sign a written informed consent form (ICF) for the study.
2. Age above 18 years inclusive at the time of signing the ICF.
3. Participants who fulfill the diagnostic criteria of myelofibrosis including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia
4. Life expectancy is greater than 6 months.
5. Subject has been receiving ruxolitinib therapy, is unlikely to benefit from further ruxolitinib monotherapy in the opinion of the investigator; AND meeting the following criteria: receiving ruxolitinib \>3 months prior to enrollment; AND stable dose for 8 weeks before starting therapy with CK0804
6. Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:
* presence of grade ≥2 anemia or thrombocytopenia or neutropenia, OR
* presence of disease-related symptoms, as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN SAF TSS) score of ≥10 points, OR
* documented splenomegaly of at least 5 cm below the costal margin as measured by physical examination or splenomegaly as documented by ultrasound or MRI.
7. Willingness to avoid pregnancy or fathering children based on the criteria below
* Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing should be communicated to the participants and their understanding confirmed.
* Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose (within 3 days of the first study treatment dose) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed,
* Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
8. ECOG performance status of 0 to 2
Exclusion Criteria:
1. Any major surgery within 28 days before the first dose of study treatment.
2. Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
3. Received chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
4. Participant has received splenic irradiation within the past 6 months.
5. Significant concurrent, uncontrolled medical condition or infections, which in the opinion of the principal investigator may interfere in the study participation.
6. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
7. Women who are pregnant or breastfeeding.
8. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
9. Participants with laboratory values at screening as defined
* Platelets \< 50 × 10\^9/L without the assistance of growth factors, thrombopoietic factors, or platelet transfusions
* ANC \< 0.5 × 10\^9/L
* ALT ≥ 2.5 × ULN
* AST ≥ 2.5 × ULN
* Direct Bilirubin \> 2.0 × ULN
* ALP ≥ 3 × ULN
* Creatinine clearance \< 50 mL/min according to Cockcroft-Gault formula.
10. Unwillingness to be transfused with blood components including RBC and platelet transfusions.
11. Inability of the participant (or parent, guardian, or legally authorized representative) to comprehend the ICF or unwillingness to sign the ICF.
1. Ability to comprehend and willingness to sign a written informed consent form (ICF) for the study.
2. Age above 18 years inclusive at the time of signing the ICF.
3. Participants who fulfill the diagnostic criteria of myelofibrosis including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia
4. Life expectancy is greater than 6 months.
5. Subject has been receiving ruxolitinib therapy, is unlikely to benefit from further ruxolitinib monotherapy in the opinion of the investigator; AND meeting the following criteria: receiving ruxolitinib \>3 months prior to enrollment; AND stable dose for 8 weeks before starting therapy with CK0804
6. Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:
* presence of grade ≥2 anemia or thrombocytopenia or neutropenia, OR
* presence of disease-related symptoms, as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN SAF TSS) score of ≥10 points, OR
* documented splenomegaly of at least 5 cm below the costal margin as measured by physical examination or splenomegaly as documented by ultrasound or MRI.
7. Willingness to avoid pregnancy or fathering children based on the criteria below
* Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing should be communicated to the participants and their understanding confirmed.
* Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose (within 3 days of the first study treatment dose) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed,
* Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
8. ECOG performance status of 0 to 2
Exclusion Criteria:
1. Any major surgery within 28 days before the first dose of study treatment.
2. Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
3. Received chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
4. Participant has received splenic irradiation within the past 6 months.
5. Significant concurrent, uncontrolled medical condition or infections, which in the opinion of the principal investigator may interfere in the study participation.
6. Inability or unlikeliness of the participant to comply with the dose schedule and study evaluations, in the opinion of the investigator.
7. Women who are pregnant or breastfeeding.
8. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
9. Participants with laboratory values at screening as defined
* Platelets \< 50 × 10\^9/L without the assistance of growth factors, thrombopoietic factors, or platelet transfusions
* ANC \< 0.5 × 10\^9/L
* ALT ≥ 2.5 × ULN
* AST ≥ 2.5 × ULN
* Direct Bilirubin \> 2.0 × ULN
* ALP ≥ 3 × ULN
* Creatinine clearance \< 50 mL/min according to Cockcroft-Gault formula.
10. Unwillingness to be transfused with blood components including RBC and platelet transfusions.
11. Inability of the participant (or parent, guardian, or legally authorized representative) to comprehend the ICF or unwillingness to sign the ICF.
Inclusion Criteria
Inclusion Criteria:
1. Ability to comprehend and willingness to sign a written informed consent form (ICF) for the study.
2. Age above 18 years inclusive at the time of signing the ICF.
3. Participants who fulfill the diagnostic criteria of myelofibrosis including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia
4. Life expectancy is greater than 6 months.
5. Subject has been receiving ruxolitinib therapy, is unlikely to benefit from further ruxolitinib monotherapy in the opinion of the investigator; AND meeting the following criteria: receiving ruxolitinib \>3 months prior to enrollment; AND stable dose for 8 weeks before starting therapy with CK0804
6. Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:
* presence of grade ≥2 anemia or thrombocytopenia or neutropenia, OR
* presence of disease-related symptoms, as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN SAF TSS) score of ≥10 points, OR
* documented splenomegaly of at least 5 cm below the costal margin as measured by physical examination or splenomegaly as documented by ultrasound or MRI.
7. Willingness to avoid pregnancy or fathering children based on the criteria below
* Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing should be communicated to the participants and their understanding confirmed.
* Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose (within 3 days of the first study treatment dose) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed,
* Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
8. ECOG performance status of 0 to 2
1. Ability to comprehend and willingness to sign a written informed consent form (ICF) for the study.
2. Age above 18 years inclusive at the time of signing the ICF.
3. Participants who fulfill the diagnostic criteria of myelofibrosis including primary myelofibrosis and myelofibrosis arising from polycythemia vera and essential thrombocythemia
4. Life expectancy is greater than 6 months.
5. Subject has been receiving ruxolitinib therapy, is unlikely to benefit from further ruxolitinib monotherapy in the opinion of the investigator; AND meeting the following criteria: receiving ruxolitinib \>3 months prior to enrollment; AND stable dose for 8 weeks before starting therapy with CK0804
6. Subject with evidence of evaluable residual burden of disease following ruxolitinib monotherapy treatment, consisting of:
* presence of grade ≥2 anemia or thrombocytopenia or neutropenia, OR
* presence of disease-related symptoms, as determined by a Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN SAF TSS) score of ≥10 points, OR
* documented splenomegaly of at least 5 cm below the costal margin as measured by physical examination or splenomegaly as documented by ultrasound or MRI.
7. Willingness to avoid pregnancy or fathering children based on the criteria below
* Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last study treatment dose and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing should be communicated to the participants and their understanding confirmed.
* Women of childbearing potential must have a negative serum pregnancy test at screening before the first dose (within 3 days of the first study treatment dose) and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through the safety follow-up visit and must not donate oocytes during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participants and their understanding confirmed,
* Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age) are eligible.
8. ECOG performance status of 0 to 2
Gender
All
Gender Based
false
Keywords
myelofibrosis
ruxolitinib
CK0804
T regulatory cells
cord blood unit
allogeneic
Treg Cells
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Myeloproliferative Disorders
Thrombocytosis
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05423691
Org Class
Industry
Org Full Name
Cellenkos, Inc.
Org Study Id
CK0804.101.1
Overall Status
Recruiting
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Phase Ib, Open-label Study of Add on Therapy With CK0804 in Participants With Myelofibrosis, With Suboptimal Response to Ruxolitinib
Primary Outcomes
Outcome Description
* severe (grade 3 or 4) infusion-related toxicity within 24 hours (NCI-CTCAE V5.0) of exposure that does not resolve with standard of care treatment within 72 hours.
* regimen related death within 28 days
* regimen related death within 28 days
Outcome Measure
To determine Treatment limiting toxicity (TLT) as defined below
Outcome Time Frame
28 days
Secondary Outcomes
Outcome Description
To determine the efficacy of CK0804 as add-on therapy in participants with myelofibrosis, with suboptimal response to ruxolitinib
Outcome Time Frame
6 months
Outcome Measure
Assessment of overall response rate (ORR) (measured as CR or PR) and its duration, using modified International Working Group-Myeloproliferative Neoplasm Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) consensus report.
Outcome Description
To determine the efficacy of CK0804 as add-on therapy in participants with myelofibrosis, with suboptimal response to ruxolitinib
Outcome Time Frame
6 months
Outcome Measure
Rate of anemia response as per modified IWG-MRT ELN response criteria.
Outcome Description
To determine the efficacy of CK0804 as add-on therapy in participants with myelofibrosis, with suboptimal response to ruxolitinib
Outcome Time Frame
6 months
Outcome Measure
Rate of spleen response by imaging at and after 24 weeks as per IWG-MRT ELN response criteria
Outcome Description
To determine the efficacy of CK0804 as add-on therapy in participants with myelofibrosis, with suboptimal response to ruxolitinib
Outcome Time Frame
6 months
Outcome Measure
Percentage of Participants who will Achieve Total Symptom Score Reduction Greater Than or Equal to (≥) 50% (TSS50) as Measured by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Swati Goel
Investigator Email
swgoel@montefiore.org
Investigator Phone
718-920-6310 / 718-920-4137