- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01161550
Cladribine Based Induction Therapy With All-Trans Retinoic Acid and Midostaurin in Relapsed/Refractory AML (CLAG ATRA AML)
Phase 1 Study of Cladribine Based Induction Therapy (CLAG) With ATRA (All-Trans Retinoic Acid) and Midostaurin in Relapsed/Refractory AML
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Missouri
-
St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient must be ≥18 of age. Because no dosing or adverse event data are currently available on the use of midostaurin in combination with ATRA and CLAG in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric phase 2 combination trials.
- Patient must be diagnosed with refractory or relapsed AML. For the purpose of the study, refractory AML is defined as failure to achieve CR after 2 cycles of induction chemotherapy or persistent > 40% bone marrow blasts after one cycle of chemotherapy induction. Relapsed AML is defined as any evidence of disease recurrence after achieving CR. Early relapse is defined as relapse occurring earlier than 12 months and late relapse is defined as relapse occurring later than 12 months.
- Patient must have a Karnofsky Performance Status of ≥ 70% (unless poor performance status is related to the disease).
Patient must have the following laboratory values:
- AST and ALT ≤ 1.5 x Upper Limit of Normal (ULN),
- Serum Bilirubin ≤ 1.5 x ULN,
- Serum Creatinine ≤ 1.5 x ULN. Laboratory values can be outside this range if secondary to AML disease.
- Patient must able to understand and willing to sign a written informed consent document prior to registration on study.
Exclusion Criteria:
- Patient must not have newly diagnosed AML.
- Patient must not have acute promyelocytic leukemia
- Patient must not have known CNS leukemia
- Patient must not have a history of allergic reactions to compounds of similar chemical or biologic composition to midostaurin or other agents used in the study.
- Patient must not have any uncontrolled or intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction within 6 months, poorly controlled hypertension, uncontrolled diabetes, chronic renal disease, or psychiatric illness/social situation that would limit compliance with study requirements.
- Patient must not have any condition, including the presence of laboratory abnormalities, which places him/her at unacceptable risk if s/he were to participate in the study or confounds the ability to interpret data from the study.
- Patient may not concurrently use other anti-cancer agents or treatments (with the exceptions of hydroxyurea, steroids, and leukopheresis).
- Female patients must not be pregnant or breastfeeding.
- Adults of reproductive potential must employ an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of midostaurin. Women considered not of childbearing potential include any of the following: no menses for at least 5 years; menses within 5 years but amenorrheic for at least 2 months and luteinizing hormone (LH) and follicular stimulating hormone (FSH) values within normal range (according to definition of postmenopausal for laboratory used); bilateral oophorectomy amenorrheic for at least 3 months.
Patient must not have impaired cardiac function including any of the following:
- Screening ECG with a QTc > 450 msec
- Patients with congenital long QT syndrome
- History or presence of sustained ventricular tachycardia
- Any history of ventricular fibrillation or torsades de pointes
- Bradycardia defined as HR < 50 bpm
- Right bundle branch block + left anterior hemiblock (bifascicular block)
- Patients with myocardial infarction or unstable angina < 6 months prior to starting study drug
- CHF NY Heart Association class III or IV
- Patients with an ejection fraction < 50% assessed by MUGA or ECHO scan within 14 days of Day 1.
- Patients must not have a known confirmed diagnosis of HIV infection or active viral hepatitis.
- Patient may not have received any investigational agent within 30 days prior to Day 1. Patient may not be receiving any other investigational agents while on this trial.
- Patients must not have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1.
- Patients must not have any pulmonary infiltrate, including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm 1
GCSF 300 mcg SC Days 1-6 Cladribine 5 mg/m2 IV Days 2-6 Cytarabine 2 mg/m2 IV Days 2-6 ATRA 15 mg/m2 PO QD Days 7-20 Midostaurin 25 mg PO BID Days 7-20 |
Other Names:
Other Names:
Other Names:
Other Names:
Other Names:
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EXPERIMENTAL: Arm 2
GCSF 300 mcg SC Days 1-6 Cladribine 5 mg/m2 IV Days 2-6 Cytarabine 2 mg/m2 IV Days 2-6 ATRA 15 mg/m2 PO QD Days 7-20 Midostaurin 50 mg PO BID Days 7-20 |
Other Names:
Other Names:
Other Names:
Other Names:
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Tolerability of midostaurin + ATRA given with CLAG chemotherapy
Time Frame: 28 days following completion of therapy
|
28 days following completion of therapy
|
Dose limiting toxicity (DLT) of midostaurin + ATRA with CLAG chemotherapy
Time Frame: 28 days following completion of therapy
|
28 days following completion of therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response
Time Frame: 1 year
|
To determine the response rate 3, morphologic leukemia-free state, morphologic complete remission rate (CRm), cytogenetic CR (CRc) rate, CR with incomplete blood counts 1 rate, and partial remission 48 rate (PR) of patients treated with midostaurin + ATRA given with CLAG chemotherapy
|
1 year
|
Survival
Time Frame: 1 year
|
To determine the duration of response and survival including disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) in these patients
|
1 year
|
Toxicity profile of midostaurin + ATRA
Time Frame: 28 days following completion of treatment
|
28 days following completion of treatment
|
|
Pharmacokinetics of midostaurin
Time Frame: Cycle 1 Day 7, Cycle 1 Day 14, and Cycle 1 Day 20
|
Cycle 1 Day 7, Cycle 1 Day 14, and Cycle 1 Day 20
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Protein Kinase Inhibitors
- Adjuvants, Immunologic
- Keratolytic Agents
- Lenograstim
- Cytarabine
- Cladribine
- Tretinoin
- Midostaurin
Other Study ID Numbers
- 10-1181 / 201108160
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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