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Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia | Clinical Trials | Clareo Health

COMPLETEDPHASE1

Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

Phase I Study of the Combination of Midostaurin, Bortezomib, and Chemotherapy in Relapsed/Refractory Acute Myeloid Leukemia

NCT01174888•Alison Walker

View on ClinicalTrials.gov

Summary

RATIONALE: Bortezomib and midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and midostaurin together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with midostaurin with or without combination chemotherapy in treating patients with relapsed or refractory acute myeloid leukemia.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of bortezomib in combination with midostaurin and intensive chemotherapy in patients with relapsed/refractory acute myeloid leukemia (AML). II. To define the specific toxicities and the dose limiting toxicity (DLT) of midostaurin and bortezomib in combination with intensive chemotherapy in relapsed/refractory AML. SECONDARY OBJECTIVES: I. To determine the rate of complete remission (CR) of midostaurin and bortezomib in combination with intensive chemotherapy. II. To determine the overall response rate (ORR). III. To characterize the biological activity of midostaurin and bortezomib to potentially increase endogenous phosphatase activity and therefore inhibit aberrant tyrosine kinases by assessing FLT3 and KIT tyrosine kinase activity as well as SHP-1(Anti-Src Homology Phosphatase-1)phosphatase activity. IV. To correlate the biological activity of midostaurin and bortezomib to potentially increase endogenous phosphatase activity with clinical response. V. To conduct pharmacokinetic studies of midostaurin and bortezomib together and in combination with intensive chemotherapy. VI. To determine the efficacy of midostaurin and bortezomib in combination with intensive chemotherapy at the maximum tolerated dose in patients with FLT3 or KIT tyrosine kinase mutations. OUTLINE: This is a dose escalation study of bortezomib. Patients are assigned to 1 of 2 treatment groups. GROUP I (Dose levels 1-2): Patients receive oral midostaurin twice daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. GROUP II (Dose levels 3-6): Patients receive mitoxantrone hydrochloride IV over 10 minutes, etoposide IV over 1 hour, and cytarabine IV over 6 hours on days 1-6. Patients also receive oral midostaurin twice daily on days 8-21 and bortezomib IV on days 8, 11, 15, and 18. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients age \>18 with relapsed or refractory acute myeloid leukemia by WHO criteria are eligible for dose levels 1 and 2. Patients age \>18 and ≤ 70 with relapsed or refractory acute myeloid leukemia by WHO criteria are eligible for dose levels 3 through 6. Patients with secondary AML are eligible
•If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
•Eastern Cooperative Oncology Group (ECOG) performance status \<2
•Patients must have adequate organ function as defined below:
•* total bilirubin \<2.0mg/dL or ≤1.5 ULN(institutional upper limit of normal)
•* AST(aspartate aminotransferase)(SGOT)/ALT(Alanine aminotransferase) (SGPT) \<2.5 X institutional ULN
•* creatinine \<1.7 mg /dL

Exclusion Criteria

•Ability to understand and willingness to sign the written informed consent document
•Patients must have recovered from the toxicity of prior therapy to less than Grade 2
•Patients status post prior hematopoietic stem cell transplantation are eligible
•Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Hydroxyurea may be administered until initiation of treatment on the study
•Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
•Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
•Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to midostaurin, bortezomib, mitoxantrone, etoposide or cytarabine that are not easily managed. Patient has a hypersensitivity to bortezomib, boron, or mannitol.
•Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
•Ejection fraction \<50%
•Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study.
+7 more criteria

Locations (1)

The Ohio State University Medical Center

Columbus, Ohio, United States

Key Dates

Start Date

August 1, 2010

Primary Completion Date

April 1, 2014

Completion Date

May 1, 2016

Last Updated

July 6, 2016

Enrollment

ACTUAL participants

Conditions

Acute Myeloid LeukemiaAcute Myeloid Leukemia With Multilineage Dysplasia FollowingMyelodysplastic SyndromeAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)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)Recurrent Adult Acute Myeloid LeukemiaSecondary Acute Myeloid Leukemia

Interventions

midostaurin

DRUG

Bortezomib

DRUG

mitoxantrone hydrochloride

DRUG

etoposide

DRUG

cytarabine

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 6, 2016Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria

Exclusion Criteria

Phase I Study of HC-7366 for Acute Myeloid Leukemia

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