Leukemia, Myeloid, AcutePhase 1CLAG ATRA AMLNCT01161550
Cladribine Based Induction Therapy With All-Trans Retinoic Acid and Midostaurin in Relapsed/Refractory AML
A Phase 1 study testing Granulocyte colony-stimulating factor (G-CSF), Cladribine and Cytarabine in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This study will evaluate the investigational drug Midostaurin in various doses given with ATRA and CLAG chemotherapy. Midostaurin is a FLT3 inhibitor that is activated or overexpressed in a significant proportion of AML patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Granulocyte colony-stimulating factor (G-CSF), Cladribine and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Aug 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase 1 Study of Cladribine Based Induction Therapy (CLAG) With ATRA (All-Trans Retinoic Acid) and Midostaurin in Relapsed/Refractory AML
This study will evaluate the investigational drug Midostaurin in various doses given with ATRA and CLAG chemotherapy. Midostaurin is a FLT3 inhibitor that is activated or overexpressed in a significant proportion of AML patients. Research has shown that midostaurin and drugs like midostaurin may work better in combination with chemotherapy, like CLAG. CLAG is a combination of cladribine, cytarabine, and G-CSF which is approved by the FDA and used to treat AML.
Read the detailed description
The main purpose of this study is to gather information about the use of a drug called midostaurin when given with ATRA and CLAG chemotherapy. Midostaurin is an investigational drug. It is a drug that inhibits FLT3 that is mutated or overexpressed in a significant proportion of AML patients. Research has shown that midostaurin and drugs like midostaurin may work better in combination with chemotherapy, like CLAG. ATRA is known to promote myeloid differentiation and has also been shown to augment cancer cell death in combination with chemotherapy. CLAG is a combination of cladribine, cytarabine, and G-CSF which is approved by the FDA and used to treat AML. This study will look at how safe this combination is, how you tolerate the treatment, and to see what dose of midostaurin is appropriate.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Granulocyte colony-stimulating factor (G-CSF), Cladribine, Cytarabine, All-Trans Retinoic Acid (ATRA), Midostaurin
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Granulocyte colony-stimulating factor (G-CSF)Drug
Also called Filgrastim
CladribineDrug
Also called Litak, Movectro
CytarabineDrug
Also called Cytosar-U, Depocyt
All-Trans Retinoic Acid (ATRA)Drug
Also called Tretinoin
MidostaurinDrug
Also called PKC412
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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 Receives: Drug: Granulocyte colony-stimulating factor (G-CSF); Drug: Cladribine; Drug: Cytarabine; Drug: All-Trans Retinoic Acid (ATRA); Drug: Midostaurin |
| Arm 2 | Experimental | 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 Receives: Drug: Granulocyte colony-stimulating factor (G-CSF); Drug: Cladribine; Drug: Cytarabine; Drug: All-Trans Retinoic Acid (ATRA); Drug: Midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of midostaurin + ATRA given with CLAG chemotherapy
Measured: 28 days following completion of therapy
Dose limiting toxicity (DLT) of midostaurin + ATRA with CLAG chemotherapy
Measured: 28 days following completion of therapy
Secondary outcomes (4)
Response
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
Measured: 1 year
Survival
To determine the duration of response and survival including disease-free survival (DFS), event-free survival (EFS), and overall survival (OS) in these patients
Measured: 1 year
Toxicity profile of midostaurin + ATRA
Measured: 28 days following completion of treatment
Pharmacokinetics of midostaurin
Measured: Cycle 1 Day 7, Cycle 1 Day 14, and Cycle 1 Day 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2010 (estimated)
- Study startNov 2010
- Primary completionAug 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Camille Abboud, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01161550
- Sponsor's protocol ID
- 10-1181 / 201108160
- Acronym
- CLAG ATRA AML
- Status last verified
- Jul 2013
- First submitted
- 9 Jul 2010
- Last updated
- 23 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Ramsingh G, Westervelt P, McBride A, Stockerl-Goldstein K, Vij R, Fiala M, Uy G, Cashen A, Dipersio JF, Abboud CN. Phase I study of cladribine, cytarabine, granulocyte colony stimulating factor (CLAG regimen) and midostaurin and all-trans retinoic acid in relapsed/refractory AML. Int J Hematol. 2014 Mar;99(3):272-8. doi: 10.1007/s12185-014-1503-4. Epub 2014 Feb 2.
PubMed 24488798
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Cladribine Based Induction Therapy (CLAG) With ATRA (All-Trans Retinoic Acid) and Midostaurin in Relapsed/Refractory AML
- ClinicalTrials.gov ID
- NCT01161550
- Acronym / sponsor ID
- CLAG ATRA AML / 10-1181 / 201108160
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 13 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the investigational drug Midostaurin in various doses given with ATRA and CLAG chemotherapy. Midostaurin is a FLT3 inhibitor that is activated or overexpressed in a significant proportion of AML patients. Research has shown that midostaurin and drugs like midostaurin may work better in combination with chemotherapy, like CLAG. CLAG is a combination of cladribine, cytarabine, and G-CSF which is approved by the FDA and used to treat AML.
Detailed description
The main purpose of this study is to gather information about the use of a drug called midostaurin when given with ATRA and CLAG chemotherapy. Midostaurin is an investigational drug. It is a drug that inhibits FLT3 that is mutated or overexpressed in a significant proportion of AML patients. Research has shown that midostaurin and drugs like midostaurin may work better in combination with chemotherapy, like CLAG. ATRA is known to promote myeloid differentiation and has also been shown to augment cancer cell death in combination with chemotherapy. CLAG is a combination of cladribine, cytarabine, and G-CSF which is approved by the FDA and used to treat AML. This study will look at how safe this combination is, how you tolerate the treatment, and to see what dose of midostaurin is appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Granulocyte colony-stimulating factor (G-CSF), Drug: Cladribine, Drug: Cytarabine, Drug: All-Trans Retinoic Acid (ATRA), Drug: MidostaurinGCSF 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 |
| Arm 2 | Experimental | Drug: Granulocyte colony-stimulating factor (G-CSF), Drug: Cladribine, Drug: Cytarabine, Drug: All-Trans Retinoic Acid (ATRA), Drug: MidostaurinGCSF 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- Patient must able to understand and willing to sign a written informed consent document prior to registration on study.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Granulocyte colony-stimulating factor (G-CSF)Also: Filgrastim | Drug | Arm 1, Arm 2 |
| CladribineAlso: Litak, Movectro | Drug | Arm 1, Arm 2 |
| CytarabineAlso: Cytosar-U, Depocyt | Drug | Arm 1, Arm 2 |
| All-Trans Retinoic Acid (ATRA)Also: Tretinoin | Drug | Arm 1, Arm 2 |
| MidostaurinAlso: PKC412 | Drug | Arm 1, Arm 2 |
Primary outcome
Tolerability of midostaurin + ATRA given with CLAG chemotherapy
Time frame: 28 days following completion of therapy
Dose limiting toxicity (DLT) of midostaurin + ATRA with CLAG chemotherapy
Time frame: 28 days following completion of therapy
4 secondary outcomes
Response
Time frame: 1 year
Survival
Time frame: 1 year
Toxicity profile of midostaurin + ATRA
Time frame: 28 days following completion of treatment
Pharmacokinetics of midostaurin
Time frame: Cycle 1 Day 7, Cycle 1 Day 14, and Cycle 1 Day 20
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2013.
- Derived from this study: PubMed 24488798Ramsingh G, Westervelt P, McBride A, Stockerl-Goldstein K, Vij R, Fiala M, Uy G, Cashen A, Dipersio JF, Abboud CN. Phase I study of cladribine, cytarabine, granulocyte colony stimulating factor (CLAG regimen) and midostaurin and all-trans retinoic acid in relapsed/refractory AML. Int J Hematol. 2014 Mar;99(3):272-8. doi: 10.1007/s12185-014-1503-4. Epub 2014 Feb 2.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camille Abboud, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Granulocyte colony-stimulating factor (G-CSF), Cladribine and Cytarabine in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerability of midostaurin + ATRA given with CLAG chemotherapy (time frame: 28 days following completion of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01161550, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2013.