Conditions: Acute Myeloid Leukemia Myelodysplastic Syndromes
Keywords: AML MDS high risk myelodysplastic syndrome
Allocation: RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 144
Healthy volunteers: no

Brief summary:
CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.

Detailed description:

Arms:
arm 1: Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity. arm 2: Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity. arm 3: Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity. arm 4: Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity. arm 5: Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity. arm 6: Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity. arm 7: Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent. arm 8: Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity. arm 9: Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Interventions: intervention 1: Itraconazole intervention 2: PKC412
Intervention descriptions: intervention 1: Itraconazole was commercially available. intervention 2: PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

Protocol document: