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A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytarabine for Consolidation in Patients With Acute Myeloid Leukemia (AML)


Phase 1
18 Years
60 Years
Not Enrolling
Both
Acute Myeloid Leukemia (AML)

Thank you

Trial Information

A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytarabine for Consolidation in Patients With Acute Myeloid Leukemia (AML)


OBJECTIVES:

Primary

- Determine the safety and tolerability of PKC412 administered sequentially or
concurrently with induction chemotherapy comprising daunorubicin and cytarabine
followed by consolidation therapy comprising high-dose cytarabine in patients with
newly diagnosed acute myeloid leukemia.

- Compare the pharmacokinetics of these regimens in these patients.

Secondary

- Determine the efficacy of these regimens, in terms of response rate, disease-free
survival, and overall survival, in these patients.

- Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target
genes with response in patients treated with these regimens.

OUTLINE: This is an open-label, multicenter study. Patients are alternately assigned to 1 of
2 induction treatment groups.

- Induction therapy:

- Group I (sequential therapy): Patients receive daunorubicin IV over 30 minutes on
days 1-3, cytarabine IV continuously on days 1-7, and oral PKC412 twice daily on
days 8-21 in the absence of disease progression or unacceptable toxicity.

- Group II (concurrent therapy): Patients receive daunorubicin and cytarabine as in
group I and oral PKC412 twice daily on days 1-7 and 15-21 in the absence of
disease progression or unacceptable toxicity.

In both groups, patients are evaluated on day 28. Patients with persistent disease receive a
second induction course comprising daunorubicin IV over 30 minutes on days 1 and 2,
cytarabine IV continuously on days 1-5, and oral PKC412 on the same schedule as their
assigned treatment group. Patients with a complete response after course 1 or course 2
proceed to consolidation therapy.

- Consolidation therapy: Patients in both groups receive high-dose cytarabine IV over 3
hours twice daily on days 1, 3, and 5 and oral PKC412 on the same schedule as their
assigned treatment group. Treatment repeats every 28-42 days for 3 courses in the
absence of disease progression or unacceptable toxicity.

After completion of consolidation therapy, patients in both groups continue to receive
PKC412 alone, according to their assigned treatment group, every 28-42 days for up to 3
years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed acute myeloid leukemia (AML)

- Newly diagnosed disease

- No history of or newly diagnosed myelodysplastic syndromes, history of
myeloproliferative disease, or secondary AML

- No CNS malignancy

PATIENT CHARACTERISTICS:

Age

- 18 to 60

Performance status

- Karnofsky 70-100%

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- AST and ALT ≤ 1.5 times upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- No active viral hepatitis

Renal

- Creatinine ≤ 1.5 times ULN

- No chronic renal disease

Cardiovascular

- Ejection fraction ≥ 50% by MUGA or echocardiogram

- No congestive heart failure

- No myocardial infarction within the past 6 months

- No poorly controlled hypertension

- No other cardiovascular disease

Pulmonary

- No pulmonary infiltrate, including those suspected to be infectious

- Patients with pulmonary infection whose clinical symptoms have resolved are
eligible provided there are no residual pulmonary infiltrates on chest x-ray

Other

- No gastrointestinal impairment or disease that would preclude absorption of study
drugs

- No uncontrolled diabetes

- No active uncontrolled infection

- No other disease, except carcinoma in situ, that would preclude study participation

- No other severe or uncontrolled medical condition that would preclude study
participation

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 5 days since prior growth factors

- No concurrent biological response modifiers

Chemotherapy

- No prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy except radiation castration

- No concurrent radiotherapy

Surgery

- More than 14 days since prior surgical procedure except central venous catheter
placement or other minor procedure (e.g., skin biopsy)

Other

- More than 30 days since prior investigational agents

- No other concurrent anticancer agents

- No other concurrent investigational drugs

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Ronald Paquette, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NOVARTIS-CPKC412A2106

NCT ID:

NCT00093600

Start Date:

February 2004

Completion Date:

June 2011

Related Keywords:

  • Acute Myeloid Leukemia (AML)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • untreated adult acute myeloid leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781
MD Anderson Cancer Center/University of TexasHouston, Texas  77030
Dana Faber Cancer InstituteBoston, Massachusetts  02115
Wayne State University/Karmanos Cancer InstituteDetroit, Michigan  48201