A Study of CBX-250 in Participants With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
A Study of CBX-250 in Participants With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Study CBX-250-001 is a Phase 1, open-label, dose-escalation study of CBX-250 in participants with relapsed/refractory AML, HR-MDS and CMML. Participants aged 12 years are planned to be enrolled. CBX-250 will initially be investigated on a fixed step-up dosing schedule. CBX-250 will be administered subcutaneously in 28-day cycles, with the first study drug dose administered on Cycle 1, Day 1. Cycle 1 will consist of a priming phase over 7 days, and a target phase over 28 days. Participants will continue CBX-250 until progressive disease (PD) or unacceptable toxicity. All subsequent treatment cycles will be 28 days.
Leukemia,
Myelodysplastic Syndrome
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics
CBX-250
Ball, Somedeb
National
Vanderbilt University
09-05-2025
Eligibility
12 Years and older
ALL
false
Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
Age
1. Dose Escalation: Male or female participants aged 18 years.
1. Dose Escalation: Male or female participants aged 18 years.
2. Backfill Cohorts: Male or female participants aged 12 years for whom no curative treatment options, including transplantation, are available. Diagnosis \& Disease Characteristics
2. Backfill Cohorts: Male or female participants aged 12 years for whom no curative treatment options, including transplantation, are available. Diagnosis \& Disease Characteristics
3. Participants with histological confirmation of advanced hematologic malignancy including: 1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. 2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
3. Participants with histological confirmation of advanced hematologic malignancy including: 1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. 2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
4. White blood cells must be below 25,000/L at time of enrollment. Participants may receive cytoreduction prior to enrollment.
4. White blood cells must be below 25,000/L at time of enrollment. Participants may receive cytoreduction prior to enrollment.
5. Historical documented evidence of HLA-A\*02:01 allele positivity. Performance Level
5. Historical documented evidence of HLA-A\*02:01 allele positivity. Performance Level
6. ECOG PS score 0-1 (if aged 18 years); Karnofsky Performance Scale of 70 (if aged 16 years and 18 years); Lansky PS of 70 (if aged 16 years). Prior Therapy
6. ECOG PS score 0-1 (if aged 18 years); Karnofsky Performance Scale of 70 (if aged 16 years and 18 years); Lansky PS of 70 (if aged 16 years). Prior Therapy
7. Any prior treatment-related toxicities resolved to Grade 1 prior to enrollment, with the exception of Grade 2 alopecia.
7. Any prior treatment-related toxicities resolved to Grade 1 prior to enrollment, with the exception of Grade 2 alopecia.
8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or 50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or 50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions: * Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval. * Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions: * Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval. * Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or Grade 1.
13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or Grade 1.
14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to 10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. Adequate Organ Function Requirements within 10 Days of Treatment Initiation
14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to 10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. Adequate Organ Function Requirements within 10 Days of Treatment Initiation
15. Estimated glomerular filtration rate 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults). 1. Participants 18 years: glomerular filtration rate 45 mL/min 2. Participants 18 years: 45 mL/min x (participant's body surface area m2/1.73) Adequate liver function defined as: * Total bilirubin 1.5 the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician). Sex and Contraceptive/Barrier Requirements
15. Estimated glomerular filtration rate 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults). 1. Participants 18 years: glomerular filtration rate 45 mL/min 2. Participants 18 years: 45 mL/min x (participant's body surface area m2/1.73) Adequate liver function defined as: * Total bilirubin 1.5 the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician). Sex and Contraceptive/Barrier Requirements
16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. Informed Consent
17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. Informed Consent
18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.
18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Participants are excluded from the study if any of the following criteria apply:
Diagnosis
Diagnosis
1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
2. Isolated extramedullary relapse.
2. Isolated extramedullary relapse.
3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy). Infection
3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy). Infection
4. Known HIV infection.
4. Known HIV infection.
5. Active hepatitis B infection (participants with documented clearance following treatment are allowed).
5. Active hepatitis B infection (participants with documented clearance following treatment are allowed).
6. Active hepatitis C infection (participants with documented clearance following treatment are allowed). Pregnancy and Breastfeeding
6. Active hepatitis C infection (participants with documented clearance following treatment are allowed). Pregnancy and Breastfeeding
7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Concurrent Conditions
7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Concurrent Conditions
8. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class >II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) >480 msec
8. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class >II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) >480 msec
9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. Concomitant Medications and Interventions
11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. Concomitant Medications and Interventions
12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
15. Known allergy or sensitivity to study drug, including excipients.
15. Known allergy or sensitivity to study drug, including excipients.
Participants are eligible to be included in the study only if all of the following criteria apply:
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
Age
1. Dose Escalation: Male or female participants aged 18 years.
1. Dose Escalation: Male or female participants aged 18 years.
2. Backfill Cohorts: Male or female participants aged 12 years for whom no curative treatment options, including transplantation, are available. Diagnosis \& Disease Characteristics
2. Backfill Cohorts: Male or female participants aged 12 years for whom no curative treatment options, including transplantation, are available. Diagnosis \& Disease Characteristics
3. Participants with histological confirmation of advanced hematologic malignancy including: 1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. 2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
3. Participants with histological confirmation of advanced hematologic malignancy including: 1. R/R AML, as defined by standardized criteria (e.g., European LeukemiaNet criteria \[Dohner 2022\]; after standard of care therapy. Participants with persistent leukemia after initial therapy or with recurrence of leukemia at any time after achieving a response during or after the course of treatment (including HSCT) are eligible. 2. R/R HR-MDS or very high risk MDS as per the Revised International Prognostic Scoring System (IPSS-R; Greenberg 2012) or Molecular International Prognostic Scoring System (IPPS-M, Bernard 2022) who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine). 3. R/R CMML who are resistant or refractory to 4-6 cycles of hypomethylating agents (HMA; decitabine or azacitidine).
4. White blood cells must be below 25,000/L at time of enrollment. Participants may receive cytoreduction prior to enrollment.
4. White blood cells must be below 25,000/L at time of enrollment. Participants may receive cytoreduction prior to enrollment.
5. Historical documented evidence of HLA-A\*02:01 allele positivity. Performance Level
5. Historical documented evidence of HLA-A\*02:01 allele positivity. Performance Level
6. ECOG PS score 0-1 (if aged 18 years); Karnofsky Performance Scale of 70 (if aged 16 years and 18 years); Lansky PS of 70 (if aged 16 years). Prior Therapy
6. ECOG PS score 0-1 (if aged 18 years); Karnofsky Performance Scale of 70 (if aged 16 years and 18 years); Lansky PS of 70 (if aged 16 years). Prior Therapy
7. Any prior treatment-related toxicities resolved to Grade 1 prior to enrollment, with the exception of Grade 2 alopecia.
7. Any prior treatment-related toxicities resolved to Grade 1 prior to enrollment, with the exception of Grade 2 alopecia.
8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or 50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
8. Radiation Therapy: At least 60 days from prior total body irradiation, craniospinal radiation and/or 50% radiation of the pelvis, or at least 14 days from local palliative radiation therapy (small port).
9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
9. Stem Cell Infusion: At least 60 days must have elapsed from HSCT and at least 4 weeks (from first dose) must have elapsed from donor lymphocyte infusion without conditioning.
10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
10. Immunotherapy: At least 42 days since prior immunotherapy, including tumor vaccines and checkpoint inhibitors, and at least 21 days since receipt of chimeric antigen receptor therapy.
11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions: * Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval. * Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
11. Anti-Leukemia Therapy: At least 14 days since the completion of anti-leukemic therapy (for example, but not limited to, small molecule or cytotoxic/myelosuppressive therapy), with the following exceptions: * Hydroxyurea for cytoreduction can be initiated without restriction related to timing of study entry. Hydroxyurea for cytoreduction can be continued concomitantly with CBX-250, with Study Responsible Physician approval. * Intrathecal chemotherapy at the time of diagnostic lumbar puncture at least 24 hours prior to the start of CBX-250 and may continue prophylactic intrathecal chemotherapy beginning in Cycle 2, at the treating physician's discretion.
12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
12. Hematopoietic Growth Factors: At least 7 days since the completion of therapy with short-acting hematopoietic growth factors and 14 days with long-acting growth factors.
13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or Grade 1.
13. Biologics (e.g. monoclonal antibody therapy): At least 28 days or 5 half-lives, whichever is shorter, have elapsed since the completion of therapy with a biologic agent. Any AE related to prior biologic treatment must be resolved to baseline severity or Grade 1.
14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to 10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. Adequate Organ Function Requirements within 10 Days of Treatment Initiation
14. Steroids: At least 7 days since systemic glucocorticoid therapy, unless receiving physiologic dosing (equivalent to 10 mg prednisone daily) or cytoreductive therapy. Cytoreductive therapy must have approval of the Study Responsible Physician. Adequate Organ Function Requirements within 10 Days of Treatment Initiation
15. Estimated glomerular filtration rate 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults). 1. Participants 18 years: glomerular filtration rate 45 mL/min 2. Participants 18 years: 45 mL/min x (participant's body surface area m2/1.73) Adequate liver function defined as: * Total bilirubin 1.5 the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician). Sex and Contraceptive/Barrier Requirements
15. Estimated glomerular filtration rate 45 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric participants or Cockcroft-Gault formula for adults). 1. Participants 18 years: glomerular filtration rate 45 mL/min 2. Participants 18 years: 45 mL/min x (participant's body surface area m2/1.73) Adequate liver function defined as: * Total bilirubin 1.5 the upper limit of normal (ULN) for age or normal conjugated bilirubin, or total bilirubin 3.0 x ULN with direct bilirubin within normal range in participants with well documented Gilbert's syndrome or hemolysis or who require regular blood transfusions. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 ULN (unless attributed to leukemic involvement with discussion with the Study Responsible Physician). Sex and Contraceptive/Barrier Requirements
16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
16. If a female of childbearing potential, willing to use a highly effective method of contraception or double barrier method from the time of enrollment through 120 days following the last study drug dose.
17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. Informed Consent
17. If male of childbearing potential, agrees to use barrier contraception from the time of enrollment through 120 days following the last study drug dose. Informed Consent
18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.
18. Participant or participant's health care proxy is able and willing to provide written informed consent and able to follow study instructions.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Participants are excluded from the study if any of the following criteria apply:
Diagnosis
Diagnosis
1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
1. Previous CTSG targeted therapy or treatment with any pMHC T-cell engager.
2. Isolated extramedullary relapse.
2. Isolated extramedullary relapse.
3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy). Infection
3. Active central nervous system (CNS) disease. Participants with prior CNS history can be enrolled if the participant has a negative lumbar puncture following completion of intrathecal chemotherapy). Infection
4. Known HIV infection.
4. Known HIV infection.
5. Active hepatitis B infection (participants with documented clearance following treatment are allowed).
5. Active hepatitis B infection (participants with documented clearance following treatment are allowed).
6. Active hepatitis C infection (participants with documented clearance following treatment are allowed). Pregnancy and Breastfeeding
6. Active hepatitis C infection (participants with documented clearance following treatment are allowed). Pregnancy and Breastfeeding
7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Concurrent Conditions
7. Pregnant or nursing women: Negative serum pregnancy tests are required during Screening and a negative serum or urine pregnancy test is required within 72 hours prior to receiving the first study drug administration, in females of childbearing potential. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Concurrent Conditions
8. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class >II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) >480 msec
8. Cardiac Disease: * Any of the following within the 6 months prior to study entry: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (New York Heart Association Classification Class >II), life-threatening, uncontrolled arrhythmia, cerebrovascular accident, or transient ischemic attack. * QTc using Fridericia's correction (QTcF) >480 msec
9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
9. Graft-Versus-Host Disease (GVHD): Active acute or chronic GVHD requiring systemic treatment with immunosuppressive medication. Participants may be on physiological doses of steroids.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
10. Concurrent malignancy in the previous 2 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ, melanoma in situ) treated with potentially curative therapy. Concurrent malignancy must be in CR or no evidence of disease (NED) during this timeframe.
11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. Concomitant Medications and Interventions
11. History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate. Concomitant Medications and Interventions
12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
12. Any commercially available or investigational anti-leukemic therapy other than CBX-250, with the following exceptions: Intrathecal chemotherapy for CNS prophylaxis is permitted after C1 is complete, at the treating physician's discretion.
13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
13. Participation in another therapeutic interventional clinical study in which an investigational agent was administered within 14 days or 5-halflives, whichever is shorter, of starting CBX-250. Participants may continue with non-interventional follow-up from previous clinical studies.
14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
14. Any concurrent systemic treatment to prevent GVHD. Topical treatments for GVHD are permitted.
15. Known allergy or sensitivity to study drug, including excipients.
15. Known allergy or sensitivity to study drug, including excipients.
