Study: NCT03013998

Intervention type: BIOLOGICAL
Group type: EXPERIMENTAL
Intervention: Samalizumab (BAML-16-001-S1)
Description: 300 mg/m2, IV, on days 1, 3, and 24; followed by 300 mg/m2, IV, every 21 days for 2 years in the absence of toxicity or disease progression. Dose may be de-escalated to 150 mg/m2 or escalated to 600 mg/m2 based on occurrence of dose-limiting toxicity.

Intervention type: BIOLOGICAL
Group type: EXPERIMENTAL
Intervention: BI 836858 (BAML-16-001-S2)
Description: 20 mg/m2, IV, on days 9, 16, and 23 of a 28-day cycle; followed 20 by mg/m2, IV, on days 1, 8, 15 and 22 of each 28-day cycle for 2 years in the absence of toxicity or disease progression (reduced to monthly administration in event of complete response or complete response with incomplete blood count recovery). Dose may be escalated to a maximum dose of 320 mg/m2 or de-escalated to 10 mg/m2 based on occurrence of dose-limiting toxicity.

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Laboratory Biomarker Analysis
Description: Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Daunorubicin (BAML-16-001-S1)
Description: 60 mg/m2, IV, on days 4, 5, and 6 of the induction cycle

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cytarabine (BAML-16-001-S1)
Description: 100 mg/m2, IV, on days 4 through 10 of the 24-day induction cycle; 1000 mg/m2, IV, on days 2, 4, and 6 of the consolidation cycle 1 and days 1, 3, and 5 of consolidation cycles 2 through 4

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S2)
Description: 75 mg/m2, IV, on days 1 through 7 of each 28-day cycle for 2 years in the absence of toxicity or disease progression

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: AG-221 (BAML-16-001-S3)
Description: 100 mg, oral, daily until time of intolerance or disease progression. Dose may be de-escalated to 50 mg based on occurrence of dose-limiting toxicity.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S3)
Description: 75 mg/m2, IV or SC, on days 1 through 7 of each 28-day cycle starting with cycle 6 and ending after 12 cycles for patients not attaining complete remission or complete remission with incomplete blood count recovery after 5 cycles of monotherapy with AG-221

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Entospletinib (BAML-16-001-S4)
Description: 200 mg, oral, twice daily for 5 years until time of intolerance or disease progression. Dose may be escalated to 400 mg.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S4)
Description: 75 mg/m2, IV or SC, on days 1 through 7 of each 28-day cycle and continuing for 12 cycles. Treatment starts after 1 cycle of monotherapy with entospletinib for patients not attaining complete remission or complete remission with incomplete blood count recovery or after later cycles of monotherapy with entospletinib for patients with disease progression.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Entospletinib (BAML-16-001-S5)
Description: 400 mg, oral, twice daily for 2 years on study until time of intolerance or disease progression. Dose may be de-escalated to 200 mg twice daily or 200 mg once daily based on occurrence of dose-limiting toxicity.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Decitabine (BAML-16-001-S5)
Description: 20 mg/m2, IV, on days 1 through 5 or 10 of each 28-day cycle and continuing for up to 11 cycles. During the first induction cycle, and the 2nd and 3rd induction cycles if they are needed, administration occurs on days 1 through 10 of each 28-day cycle. During subsequent consolidation, decitabine is administered on days 1 through 5 of each 28-day cycle and continuing for up to 11 cycles. Duration may be reduced by 1 day based on occurrence of dose-limiting toxicity, and patients may switch to entospletinib monotherapy maintenance at any time if they develop toxicity or are unwilling to continue decitabine during consolidation therapy.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Entospletinib (BAML-16-001-S6)
Description: 400 mg, oral, twice daily for 2 years until time of intolerance or disease progression.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Daunorubicin (BAML-16-001-S6)
Description: 60 mg/m2, IV, on days 1-3 or 1-2 of each 28-day cycle for the first and second induction cycle, respectively

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cytarabine (BAML-16-001-S6)
Description: 100 mg/m2, IV, on days 1 through 7 or 1 through 5 of each 28-day cycle for the first and second induction cycle, respectively; then 1000 mg/m2 (patients ≥60 years) or 3000 mg/m2 (younger patients with creatinine clearance \>30 mL/min and \<50 mL/min), IV, every 12 hours on days 1, 3, and 5 of each 28-day cycle for up to 4 consolidation cycles

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Pevonedistat (BAML-16-001-S9)
Description: 20 mg/m2, IV, on days 1, 3, and 5 of each 28-day cycle and continuing for 24 cycles in the absence of toxicity or disease progression

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S9)
Description: 75 mg/m2, IV or SC, on days 1 through 7 or days 1 through 5 and then 8 through 9 (based on institutional guidelines) of each 28-day cycle and continuing for 12 cycles in the absence of toxicity or disease progression

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: AG-120 (BAML-16-001-S16)
Description: 500 mg, oral, daily until time of intolerance or disease progression. Dose may be de-escalated to 250 mg based on occurrence of dose-limiting toxicity.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S16)
Description: 75 mg/m2, IV or SC, on days 1 through 7 or days 1 through 5 and then 8 through 9 (based on institutional guidelines) of each 28-day cycle and continuing for 12 cycles in the absence of toxicity or disease progression

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Gilteritinib (BAML-16-001-S8 Group 1)
Description: 120 mg, oral, daily, with treatment continuing based on bone marrow results at 28 and 56 days. Patients with partial response at 28 days continue treatment for an additional 28 days. Patients with complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) at 28 or 56 days continue treatment for 5 years until time of intolerance or disease progression. Patients with less than partial response at 28 days or partial response at 28 days followed by less than CR or CRi at 56 days proceed to combination treatment with decitabine or non-study alternative.~The combination dose is 80 mg, oral, daily, for 5 years until time of intolerance or disease progression (patients who do not achieve CR or CRi after 3 cycles will discontinue study treatment). The combination dose may be escalated to 120 mg daily or de-escalated to 80 mg daily given after decitabine rather than in combination with decitabine based on absence or occurrence of dose-limiting toxicity.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Decitabine (BAML-16-001-S8 Group 1)
Description: 20 mg/m2, IV, on days 1 through 10 of each 28-day cycle and continuing for up to 3 cycles. Treatment starts after 1-2 cycles of monotherapy with gilteritinib if patients do not attain complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) with monotherapy. Patients who do not achieve CR/CRi after 3 cycles of combination therapy will discontinue study treatment. If CR or CRi is obtained with combination therapy after 3 cycles, decitabine will be administered on days 1-5 of each subsequent 28-day cycle until progression, intolerance, or patient desire to discontinue therapy.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: AZD5153 (BAML-16-001-S10)
Description: 20 mg, oral, once daily during 7-day lead-in and then on days 1 through 21 of each 28-day cycle for up to 2 years or until allogeneic stem cell transplantation, time of intolerance, or disease progression \[if the continuous administration AZD5153 on Days 1-21 of a 28-day cycle is not tolerated, an alternative schedule of 2 weeks on and 2 weeks off (i.e. AZD5153 will be administered on Days 1-14 of a 28-day cycle) will be explored\]. Dose may be de-escalated to 10 mg or escalated to 30 mg based on occurrence of dose-limiting toxicity during phase 1 dose escalation. Starting with Cycle 2, patients may receive concomitant fluconazole, isavuconazole, or posaconazole and doses adjusted to 2, 5, or 8 mg daily. The Phase 1b expansion pharmacokinetics cohort will allow for posaconazole starting at Cycle 1 with AZD5153 dose adjusted from 10, 20, or 30 mg daily to 2, 5, or 8 mg daily. Phase 2 dose will be based on Phase 1 results.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Venetoclax (BAML-16-001-S10)
Description: 400 mg, oral, on days 1 through 21 of each 28-day cycle and continuing for up to 12 cycles (for Cycle 1, day 1 dose will be 100 mg, day 2 dose 200 mg, and days 3 onward 400 mg). Starting with Cycle 2, patients may receive concomitant fluconazole or isavuconazole and daily doses adjusted to 200 mg, or posaconazole and daily doses adjusted to 70 mg. The Phase 1b expansion pharmacokinetics cohort will allow for posaconazole starting at Cycle 1 with Venetoclax dose adjusted to 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, and 70 mg on day 4 onward).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: TP-0903 (BAML-16-001-S14)
Description: 37 mg, oral, once daily on days 1 through 21 of each 28-day cycle for up to 2 years to time of intolerance or disease progression. Dose may be de-escalated to as low as 12 mg or escalated to 50 mg based on occurrence of dose-limiting toxicity during Phase 1 dose escalation. Phase 2 dose will be based on Phase 1 results.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Decitabine (BAML-16-001-S14)
Description: 20 mg/m2, IV, on days 1 through 5 or 10 of each 28-day cycle and continuing for up to 2 years to time of intolerance or disease progression. During the first induction cycle, and the 2nd and 3rd induction cycles if they are needed, administration occurs on days 1 through 10 of each 28-day cycle. During maintenance, decitabine is administered on days 1 through 5 of each 28-day cycle. Patients may switch to TP-0903 monotherapy maintenance if they develop toxicity or are unwilling to continue decitabine during maintenance therapy.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Decitabine (BAML-16-001-S8 Group 2)
Description: 20 mg/m2, IV, on days 8 through 12 of the first 35-day induction cycle, then on days 1 through 5 of subsequent 28-day cycles and continuing for up to 60 cycles, disease progression, intolerance, or patient desire to discontinue therapy.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Venetoclax (BAML-16-001-S8 Group 2)
Description: Oral dosing based on concurrent antifungal use. Dose without use of concomitant antifungal is 400mg, dose if on posaconazole is 70mg, dose if on voriconazole is 100mg, and dose if on moderate CYP3A inhibitors (ie fluconazole, isavuconazole) is 200mg continuing for up to 12 total cycles. For the 35-day induction cycle 1, dosing is days 2 through 28. For the 28-day induction cycle 2, if needed, dosing is days 1 through 21. For the 28-day consolidation cycles, dosing is days 1-15.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: AZD5991 (BAML-16-001-S18)
Description: 150 mg, IV, on days 1, 4, 8, 11, 15, and 18 of three 28-day cycles; followed by 150 mg/m2, IV, on days 1, 4, 8, and 11 of twenty-one 28-day cycles; followed by 150 mg/m2 on days 1 and 4 of each 28-day cycle until time of progression, unacceptable toxicity, death, or 57 total cycles of treatment. Dose may be escalated to a maximum dose of 400 mg or de-escalated to 100 mg based on occurrence of dose-limiting toxicity.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S18)
Description: 75 mg/m2, IV or SC, on days 1-7 or days 1-5 and 8 and 9 or days 1-2 and 5-9 (based on institutional guidelines) of each 28-day cycle until time of progression, unacceptable toxicity, death, or 57 total cycles of treatment

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: SNDX-5613 (BAML-16-001-S17)
Description: 113 mg, oral, every 12 hours on Day 1-28 of each 28-day cycle, until time of progression, unacceptable toxicity, or death. Dose may be escalated to a maximum dose of 163 mg on days 1-28 or de-escalated to 113 mg on days 1-21 based on occurrence of dose-limiting toxicity. Other possible dose escalation and de-escalation would be 163 mg on days 1-21, 75 mg on days 1-21 and 75 mg on days 1-28. Following completion of induction, patients who do not require strong CYP3A4 inhibitor antifungals will have daily doses increased for doses in range of 113-226 mg (days 1-21 or days 1-28).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S17)
Description: 75 mg/m2, IV or SC, on days 1-7 (during induction cycle/cycles) or can use alternative scheduled on days 1-5 and 8 and 9 or days 1-2 and 5-9 (based on institutional guidelines) during continued therapy cycles of each 28-day cycle until time of progression, unacceptable toxicity, or death.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Venetoclax (BAML-16-001-S17)
Description: For Cycle 1 induction, day 1 dose is 10 mg, day 2 dose 20 mg, day 3 dose is 50 mg, and day 4 onward dose is 100 mg or 70 mg depending on concomitant antifungal treatment. For Cycles 2 and 3 inductions, daily doses are 100 or 70 mg depending on concomitant antifungal treatment. During continued therapy cycles, if not on concomitant strong CYP3A4 inhibitor antifungals, 400 mg, oral, on days 1 through 28 or days 1 through 14 of each 28-day cycle until time of progression, unacceptable toxicity, or death (patients on moderate CYP3A4 inhibitor antifungals should receive 200 mg/day).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Gilteritinib (BAML-16-001-S8 Group 2)
Description: Phase 1b induction: 80-120 mg, oral, daily for day 1 up to day 28 of the 35-day induction cycle 1; then 80-120 mg, oral, daily for day 1 up to day 28 of the 28-day induction cycle 2 (induction cycle 2 administered if needed after cycle 1 based on results bone marrow evaluation). Phase 1b consolidation: 80-120 mg, oral, daily for day 1 up to day 21 of the 28-day cycles, for a total of 12 total induction and consolidation cycles. Phase 1b induction and consolidation dose and duration may be escalated or de-escalated based on occurrence of dose-limiting toxicity. Phase 2 induction and consolidation dosage to be based on results of Phase 1b. Phase 1b and 2 maintenance: 120 mg, oral, daily for 28 days of the 28-day cycles until patient is minimal residual disease negative for FLT3 based on scheduled bone marrow biopsy, progression of disease, unacceptable toxicities, or desire to discontinue therapy.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Venetoclax (BAML-16-001-S12 Arm A)
Description: 400 mg, oral, on days 1 through 28 of each 28-day cycle for up to 2 cycles or until unacceptable toxicity or death. For Cycle 1, day 1 dose is 100 mg, day 2 dose 200 mg, and day 3 onward dose is 400 mg. (Dose adjusted by anti-fungal agent use per the package insert.)

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Azacitidine (BAML-16-001-S12 Arm A)
Description: 75 mg/m2, IV or SC, on days 1-7 or days 1-5 and 8 and 9 or days 1-2 and 5-9 (based on institutional guidelines) of each 28-day cycle for up to 2 cycles or until unacceptable toxicity or death.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Venetoclax (BAML-16-001-S12 Arm B)
Description: 400 mg, oral, on days 1 through 14 of each 14-day cycle for up to 2 cycles or until unacceptable toxicity or death. For Cycle 1, day 1 dose is 100 mg, day 2 dose 200 mg, and day 3 onward dose is 400 mg. (Dose adjusted by anti-fungal agent use per the package insert.)

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azacitidine (BAML-16-001-S12 Arm B)
Description: 75 mg/m2, IV or SC, on days 1-7 or days 1-5 and 8 and 9 or days 1-2 and 5-9 (based on institutional guidelines) of each 14-day cycle for up to 2 cycles or until unacceptable toxicity or death.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: ZE46-0134 (BAML-16-001-S21)
Description: 10 mg or 50 mg oral on Days 1-28 of each 28-day cycle for up to 24 cycles. On the first day of Cycle 1, a loading dose of 30 mg to 150 mg will be administered, after which the daily maintenance dose of 10 mg to 100 mg will be administered on days 2-28 of Cycle 1. Maintenance dose continues in subsequence cycles, for up to 24 cycles total.