Study of Biomarker-Based Treatment of Acute Myeloid Leukemia

BIOLOGICAL

Samalizumab (BAML-16-001-S1)

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.

BIOLOGICAL

BI 836858 (BAML-16-001-S2)

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.

OTHER

Laboratory Biomarker Analysis

Molecular genomic assessment to assign patients to targeted therapy (sub-study) based on their specific subtype of acute myeloid leukemia

DRUG

Daunorubicin (BAML-16-001-S1)

60 mg/m2, IV, on days 4, 5, and 6 of the induction cycle

DRUG

Cytarabine (BAML-16-001-S1)

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

DRUG

Azacitidine (BAML-16-001-S2)

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

DRUG

AG-221 (BAML-16-001-S3)

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.

DRUG

Azacitidine (BAML-16-001-S3)

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

DRUG

Entospletinib (BAML-16-001-S4)

200 mg, oral, twice daily for 5 years until time of intolerance or disease progression. Dose may be escalated to 400 mg.

DRUG

Azacitidine (BAML-16-001-S4)

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.

DRUG

Entospletinib (BAML-16-001-S5)

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.

DRUG

Decitabine (BAML-16-001-S5)

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.

DRUG

Entospletinib (BAML-16-001-S6)

400 mg, oral, twice daily for 2 years until time of intolerance or disease progression.

DRUG

Daunorubicin (BAML-16-001-S6)

60 mg/m2, IV, on days 1-3 or 1-2 of each 28-day cycle for the first and second induction cycle, respectively

DRUG

Cytarabine (BAML-16-001-S6)

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

DRUG

Pevonedistat (BAML-16-001-S9)

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

DRUG

Azacitidine (BAML-16-001-S9)

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

DRUG

AG-120 (BAML-16-001-S16)

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.

DRUG

Azacitidine (BAML-16-001-S16)

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

DRUG

Gilteritinib (BAML-16-001-S8 Group 1)

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.

DRUG

Decitabine (BAML-16-001-S8 Group 1)

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.

DRUG

AZD5153 (BAML-16-001-S10)

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.

DRUG

Venetoclax (BAML-16-001-S10)

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).

DRUG

TP-0903 (BAML-16-001-S14)

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.

DRUG

Decitabine (BAML-16-001-S14)

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.

DRUG

Decitabine (BAML-16-001-S8 Group 2)

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.

DRUG

Venetoclax (BAML-16-001-S8 Group 2)

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.

DRUG

AZD5991 (BAML-16-001-S18)

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.

DRUG

Azacitidine (BAML-16-001-S18)

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

DRUG

SNDX-5613 (BAML-16-001-S17)

Patients starting induction with CYP3A4 inhibitors will be dosed at 113 mg capsule or 110 mg tablet, 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 capsule or 220 mg tablet 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. Patients starting treatment without CYP3A4 inhibitors will be dosed at 276 mg capsule (270 mg tablet) or 226 mg capsule (220 mg tablet) oral, every 12 hours on Day 1-28 of each 28-day cycle. 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 capsules or 110-220 mg tablets (days 1-21 or days 1-28).

DRUG

Azacitidine (BAML-16-001-S17)

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.

DRUG

Venetoclax (BAML-16-001-S17)

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).

DRUG

Gilteritinib (BAML-16-001-S8 Group 2)

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.

DRUG

Venetoclax (BAML-16-001-S12 Arm A)

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.)

DRUG

Azacitidine (BAML-16-001-S12 Arm A)

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.

DRUG

Venetoclax (BAML-16-001-S12 Arm B)

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.)

DRUG

Azacitidine (BAML-16-001-S12 Arm B)

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.

DRUG

ZE46-0134 (BAML-16-001-S21 Group 1)

10 mg to 100 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 200 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.

DRUG

ficlatuzumab (BAML-16-001-S24)

10, 15 or 20 mg/kg IV on days 1 and 15.

DRUG

Azacitidine (BAML-16-001-S24)

75 mg/m2, IV or SC, on days 3-9 (during induction cycle 1) or can use alternative scheduled on days 3-7 and 10 and 11 or days 3-4 and 7-11 (based on institutional guidelines) for 30 days of Induction Cycle 1. All other induction cycle or continued therapy cycles of each 28-day cycle will be days 1-7, days 1-5 and 8-9 or days 1-2 and 5-9 (based on institutional guidelines) until time of progression, unacceptable toxicity, or death.

DRUG

Venetoclax (BAML-16-001-S24)

For Cycle 1 induction, day 3 dose is 100 mg, day 4 dose 200 mg, day 5 onward dose is 400 mg, depending on concomitant antifungal treatment. For Cycles 2 and 3 inductions, daily doses are 400mg or lower depending on concomitant antifungal treatment. During continued therapy cycles, if not on concomitant strong CYP3A4 inhibitor antifungals, 400 mg, oral, on 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).

DRUG

ZE46-0134 (BAML-16-001-S21 Group 2)

60 mg to 200 mg oral on Days 1-28 of each 28-day cycle for up to 24 cycles, for up to 24 cycles total.

Proportion of patients for whom molecular, immunophenotypic, and/or biochemical studies are completed in < 7 calendar days for assignment of treatment

Time frame: 7 days

The feasibility of completing molecular, genetic, immunophenotypic, and biochemical testing for assignment of therapy will be assessed based on the proportion of patients for whom testing is completed within 7 days of the registration sample arriving at the laboratory

Proportion of patients assigned to a novel therapeutic treatment group in 1 of several sub-studies in this Master Protocol, based on the result of the molecular, immunophenotypic, and/or biochemical studies

Time frame: 7 days

The feasibility of assigning patients to a treatment group will be assessed based on the proportion who are eligible for screening in this study who are assigned to treatment either on this study or an industry study relevant to the specific marker group and not unassignable due to insufficient material, laboratory error, or any other factors

Clinical response rate (rate of complete and partial responses) according to International Working Group criteria for treatment outcomes in therapeutic trials in acute myeloid leukemia

Time frame: Up to 5 years

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.