PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)

NCT ID: NCT00045942

Last Updated: 2017-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-30
• Study Completion Date: 2008-03-27

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PKC412 (Core)

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.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 mutated PKC412 100 mg/day (E1)

Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 mutated PKC412 200 mg/day (E1)

Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 wild type PKC412 100 mg/day (E1)

Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 wild type PKC412 200 mg/day (E1)

Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 mutated PKC412 dose escalation

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.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 mutated PKC+Itraconazole (E2)

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.

Group Type: EXPERIMENTAL

Itraconazole

Intervention Type: DRUG

Itraconazole was commercially available.

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 wild type PKC412 dose escalation (E2)

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.

Group Type: EXPERIMENTAL

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

FLT3 wild type PKC+Itraconazole (E2)

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.

Group Type: EXPERIMENTAL

Itraconazole

Intervention Type: DRUG

Itraconazole was commercially available.

PKC412

Intervention Type: DRUG

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

Interventions

Itraconazole

Itraconazole was commercially available.

Intervention Type: DRUG

PKC412

PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.

Intervention Type: DRUG

Other Intervention Names

Midostaurin

Eligibility Criteria

Inclusion Criteria

1. Patients:

with AML who are not candidates for myelosuppressive chemotherapy or with AML who have relapsed disease or are refractory to standard therapy and not likely to require cytoreductive therapy within one month or with MDS subtypes refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-T) or chronic myelomonocytic leukemia (CMML).

2. Patients with a relevant FLT3-ITD mutation or D835Y point mutation

3. Patients at least 18 years or older

4. Patients with WHO performance status of 0 to 2 with a life expectancy of at least 3 months

5. Patients must not be treated within 4 weeks after any prior therapy

6. Written informed consent obtained according to local guidelines

Exclusion Criteria

Patients meeting any of the following criteria during screening will be excluded from entry into the study:

1. Patients who had prior allogeneic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously.

2. Female patients who are pregnant or breast feeding, or adults of childbearing age not employing an effective method of birth control.

3. Concurrent severe and/or uncontrolled medical or psychiatric condition which may interfere with the completion of the study.

4. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PKC412.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

UCLA Medical Center

Los Angeles, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

New York Weill Cornell Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Other Identifiers

CPKC412A2104

Identifier Type: -

Identifier Source: org_study_id

NCT00045578

Identifier Type: -

Identifier Source: nct_alias

NCT00977782

Identifier Type: -

Identifier Source: nct_alias