Select therapeutic studies that allow MDS patient enrollment with eligibility specifying molecular features
| Mutation targeted . | Drug . | Mechanism of action . | Patient type . | Phase and trial name . | NCT identifier . |
|---|---|---|---|---|---|
| SF3B, SRSF2, U2AF1, or ZRSR2 | H3B-8800 (oral) | Inhibitor of the splicing factor SF3B1 | AML: not candidates for induction | Phase 1 Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Splicing Modulator H3B-8800 for Subjects with MDS, AML, and CMML | NCT02841540 |
| MDS: HMA refractory if higher risk or transfusion dependent if lower risk | |||||
| CMML: therapy refractory | |||||
| TET2 | Vitamin C (IV) | Mimics TET2 restoration by promoting | MDS patients with <20% blasts and platelets >20 000 (allows concurrent HMA) | Phase 1b/2a Tolerability of Vitamin C in Patients with Intermediate or High Risk MDS with TET2 Mutations | NCT03433781 |
| DNA demethylation and reversing aberrant stem cell self renewal. | |||||
| TET2 | Ascorbic acid (oral) | As above (in combination with AZA) | MDS, MDS/MPN, or AML patients who are HMA naive | Phase 2 TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia with Azacitidine + Ascorbic Acid | NCT03397173 |
| TP53 | APR-246 (IV) | Reactivate mutant p53 to induce programmed cell death | Treatment-naive myeloid neoplasm patients with <30% blasts | Phase 1b/2 Safety and Efficacy of APR-246 w/Azacitidine for tx of TP53 Mutant Myeloid Neoplasms | NCT03072043 |
| IDH2 | Enasidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH2 protein | MDS patients (up to 30% blasts) naive to HMA (arm A) or R/R to 6 cycles of HMA | Phase 2 Targeted Therapy with the IDH2-Inhibitor Enasidenib (AG221) for High-Risk IDH2-Mutant Myelodysplastic Syndrome | NCT03383575 |
| IDH1 | FT-2102 (oral) | Undefined mechanism | AML or MDS (INT, HIGH, VERY HIGH by IPSS-R) disease R/R to previous therapy | A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single Agent and in Combination with Azacitidine or Cytarabine in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome with an IDH1 Mutation | NCT02719574 |
| IDH1 R132 | Ivosidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH1 protein | R/R advanced hematologic malignancies patients | Phase 1 Study of Orally Administered AG-120 in Subjects with Advanced Hematologic Malignancies with an IDH1 Mutation | NCT02074839 |
| IDH2 | Enasidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH2 protein | R/R advanced hematologic malignancies patients (untreated arm if patients unfit) | Phase 1/2 Study of AG-221 in Subjects with Advanced Hematologic Malignancies with an IDH2 Mutation | NCT01915498 |
| IDH1 or IDH2 | AG-881 (oral) | Small-molecule mIDH1 and mIDH2 protein inhibitor; reduces the oncometabolite, 2-HG | R/R advanced hematologic malignancies patients | Study of Orally Administered AG-881 in Patients with Advanced Hematologic Malignancies with an IDH1 and/or IDH2 Mutation | NCT02492737 |
| IDH1 R132 | Venetoclax + Ivosidenib (oral) | BCL2 inhibition in combination with inhibition of mIDH1 protein | R/R AML; Patients with high-risk MDS or MPN (defined as ≥10% bone marrow blasts) may also be eligible after discussion with investigator | Study of Venetoclax with the mIDH1 Inhibitor Ivosidenib (AG120) in IDH1-Mutated Hematologic Malignancies | NCT03471260 |
| Mutation targeted . | Drug . | Mechanism of action . | Patient type . | Phase and trial name . | NCT identifier . |
|---|---|---|---|---|---|
| SF3B, SRSF2, U2AF1, or ZRSR2 | H3B-8800 (oral) | Inhibitor of the splicing factor SF3B1 | AML: not candidates for induction | Phase 1 Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Splicing Modulator H3B-8800 for Subjects with MDS, AML, and CMML | NCT02841540 |
| MDS: HMA refractory if higher risk or transfusion dependent if lower risk | |||||
| CMML: therapy refractory | |||||
| TET2 | Vitamin C (IV) | Mimics TET2 restoration by promoting | MDS patients with <20% blasts and platelets >20 000 (allows concurrent HMA) | Phase 1b/2a Tolerability of Vitamin C in Patients with Intermediate or High Risk MDS with TET2 Mutations | NCT03433781 |
| DNA demethylation and reversing aberrant stem cell self renewal. | |||||
| TET2 | Ascorbic acid (oral) | As above (in combination with AZA) | MDS, MDS/MPN, or AML patients who are HMA naive | Phase 2 TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia with Azacitidine + Ascorbic Acid | NCT03397173 |
| TP53 | APR-246 (IV) | Reactivate mutant p53 to induce programmed cell death | Treatment-naive myeloid neoplasm patients with <30% blasts | Phase 1b/2 Safety and Efficacy of APR-246 w/Azacitidine for tx of TP53 Mutant Myeloid Neoplasms | NCT03072043 |
| IDH2 | Enasidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH2 protein | MDS patients (up to 30% blasts) naive to HMA (arm A) or R/R to 6 cycles of HMA | Phase 2 Targeted Therapy with the IDH2-Inhibitor Enasidenib (AG221) for High-Risk IDH2-Mutant Myelodysplastic Syndrome | NCT03383575 |
| IDH1 | FT-2102 (oral) | Undefined mechanism | AML or MDS (INT, HIGH, VERY HIGH by IPSS-R) disease R/R to previous therapy | A Phase 1/2, Multicenter, Open-label Study of FT-2102 as a Single Agent and in Combination with Azacitidine or Cytarabine in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome with an IDH1 Mutation | NCT02719574 |
| IDH1 R132 | Ivosidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH1 protein | R/R advanced hematologic malignancies patients | Phase 1 Study of Orally Administered AG-120 in Subjects with Advanced Hematologic Malignancies with an IDH1 Mutation | NCT02074839 |
| IDH2 | Enasidenib (oral) | Reduces the oncometabolite, 2-HG through inhibition of mIDH2 protein | R/R advanced hematologic malignancies patients (untreated arm if patients unfit) | Phase 1/2 Study of AG-221 in Subjects with Advanced Hematologic Malignancies with an IDH2 Mutation | NCT01915498 |
| IDH1 or IDH2 | AG-881 (oral) | Small-molecule mIDH1 and mIDH2 protein inhibitor; reduces the oncometabolite, 2-HG | R/R advanced hematologic malignancies patients | Study of Orally Administered AG-881 in Patients with Advanced Hematologic Malignancies with an IDH1 and/or IDH2 Mutation | NCT02492737 |
| IDH1 R132 | Venetoclax + Ivosidenib (oral) | BCL2 inhibition in combination with inhibition of mIDH1 protein | R/R AML; Patients with high-risk MDS or MPN (defined as ≥10% bone marrow blasts) may also be eligible after discussion with investigator | Study of Venetoclax with the mIDH1 Inhibitor Ivosidenib (AG120) in IDH1-Mutated Hematologic Malignancies | NCT03471260 |
Current as of 30 April 2018 on clinicaltrials.gov, these trials are listed as “active” or “pending.”
2-HG, 2-hydroxyglutarate; R/R, relapsed and/or refractory.