From: Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies
NCT ID | NCT03953898 | NCT02878785 | NCT03974217 | NCT01399840 | NCT01139970 | NCT00588991 | NCT03289910 | NCT04207190 |
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Title | Using the Anticancer Drug Olaparib to Treat R/R AML or MDS With an IDH Mutation | Decitabine and Talazoparib in Untreated AML and R/R AML (1565GCC) | Talazoparib for Cohesin-Mutated AML and MDS With Excess Blasts | Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological Malignancies [172] | Veliparib and Temozolomide in Treating Patients With Acute Leukemia [160] | Veliparib and Topotecan W/Wo Carboplatin in Treating Patients With R/R Acute Leukemia, High-Risk MDS, or Aggressive MPDs | Topotecan Hydrochloride and Carboplatin W/Wo Veliparib in Treating Advanced MPDs and AML or CML [161] | Talazoparib and GO for the Treatment of CD33+ R/R AML |
Phase | 2 | 1 | 2 | 1 | 1 | 1 | 2 | 1/2 |
Number of pts | 94 | 171 | 12 | 33 | 66 | 12 | 60 | 20 |
Drug and schedule | Olaparib PO BID | Sequential dose escalation of decitabine and talazoparib, 3 + 3 design | Talazoparib, allowed HU | BMN 673 | Veliparib PO once daily QD on d 1–4 and twice daily on d 4–12 and temozolomide PO QD on d 3–9 of course 1. Beginning at least 30 d after the start of treatment, pts receive veliparib PO BID on d 1–8 and temozolomide PO QD on d 1–5. Courses. dose escalated | Veliparib when given together with topotecan hydrochloride w/wo carboplatin, doses escalated | ARM A: veliparib orally (PO) twice daily (BID) on days 1–21 and topotecan hydrochloride IV continuously over 24 h and carboplatin IV continuously over 24 h on d 3–7 ARM B: no veliparib | Pts receive talazoparib PO daily on d 1–21 and GO IV over 2 h on d 1, 4, and 7 or d 1 for pts at CR/CRi after cycles 1 or 2. Dose escalated |
Population | R/R AML | R/R AML in phase 1, new diagnosis AML unfit phase 2 | R/R AML, secondary AML or R/R MDS RAEB after aza | AML, MDS, CLL, MCL | R/R AML, R/R b-ALL, CML in accelerated/blast phase after 2 TKI, CMML-2, new onset high-risk AML > 60 y, new onset high-risk ALL > 60 y | Aggressive MPD or AML out of MPD | New onset AML secondary to MPD, R/R AML secondary to MPD, accelerated phase MPD | R/R AML |
Genetics | IDH1/2 mut | No | Cohesin mut (STAG2, SMC1A, RAD21, PDS5B, SMC3) | No | No | No | No | CD33 > 0.1% |
Endpoint | ORR | Safe dose phase 1, CR + CRi phase 2 | > 50% blast reduction | MTD | MTD | MTD | ORR | MTD phase 1; ORR extension |
Exclusion for cytopenia | No | No | No | BM cellularity < 25% for AML; MCL and CLL: platelet count < 50.000/mm3, neutrophil count < 1.000/mm3 | No | No | No | No |
Previous sct excluded | No | No | No | No | No | No | No | No |
Exclusion for hyperleuko cytosis | > 50.000 | > 50.000 | > 10.000 | > 50.000 | > 30.000 | > 50.000 | No | No |
Corrected QT exclusion criteria | > 500 | No | No | No | No | No | No | No |
Strong CYP3A4 inhibitor | Yes | No | No | No | No | No | No | No |
Safety profile for future development | Nr | Nr | Nr | Suitable | Suitable | Nr | Suitable | Nr |
Efficacy results | Nr | Nr | Nr | Stable disease in 12/24 pts. AML/MDS, 1 MDS pt. transfusion indpt | CR + CRi 16.6% (8/48); median OS = 5.3 m | Nr | ORR = 33% (14 CR, 11 CRi) | Nr |