AML
Conditions
Keywords
Leukemia
Brief summary
The study intervention involved in this study is the addition of a dose of volasertib as a part of the initial chemotherapy regimen for AML. The trial will involve a combination of the following drugs: * Volasertib (the study drug) * Idarubicin * Cytarabine
Detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. Investigational means that the drug is being studied. As part of this research study, the participant will receive Volasertib in combination with two other chemotherapy drugs, Idarubicin and Cytarabine. The FDA (the U.S. Food and Drug Administration) has not approved volasertib as a treatment for any disease. Idarubicin and Cytarabine are chemotherapy agents that are commonly used to treat individuals diagnosed with AML. Volasertib inhibits proteins called polo-like kinases, which are necessary for cell division. Volasertib binds to these proteins and this inhibits the growth of cancer cells. Volasertib has been used in laboratory studies and those studies suggest that volasertib may slow down the growth of Cancer. In a previous clinical trial in patients with the participant type of leukemia where Volasertib was given along with low doses of Cytarabine, this drug was found to have some clinical activity against AML. In this study, researchers would like to combine Volasertib with standard chemotherapy (Cytarabine and Idarubicin) in order to see if it can be given safely with chemotherapy in individuals with AML. The primary purpose of this research study is to determine the highest dose that Volasertib can be given with Idarubicin and Cytarabine without severe or unmanageable side effects. The dose identified in this study will be used in future research studies.
Interventions
DRUGVolasertib
Polo-Like Kinase Inhibitor
DRUGCytarabine
Standard chemotherapy at dosage and schedule for 7+3 induction
DRUGIdarubicin
Standard chemotherapy at dosage and schedule for 7+3 induction
PROCEDUREBone Marrow Biopsy
Bone marrow biopsy assessments scheduled during induction to assess response
Sponsors
Boehringer Ingelheim
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have pathologically confirmed, newly diagnosed acute myeloid leukemia. * Adults, age 18 years or older at the time of diagnosis, eligible for standard induction chemotherapy according to their treating physician. * ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A) * Left ventricular ejection fraction \> 50% as measured by echocardiogram or MUGA scan * Must not have received systemic antineoplastic therapy including radiation therapy within 14 days of the study enrollment, except hydroxyurea or 6-mercaptopurine for the purposes of cytoreduction as per the treating physician. Patients may also have received all-trans retinoic acid (ATRA) if there is an early suspicion of acute promyelocytic leukemia (APL, M3-AML), although if confirmed to have APL these patients will be excluded from the study. * Female patients of childbearing age must have negative pregnancy test. * Participants must have normal organ and marrow function as defined below: * total bilirubin \< 3 times the ULN * creatinine within normal institutional limits OR * creatinine clearance ≥30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal. * The effects of volasertib (BI 6727) on the developing human fetus are unknown. For this reason and because other chemotherapeutic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 6 months after completion of therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study participation, and 6 months after completion of therapy. * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Patients will be excluded from this study if they are found to harbor favorable risk cytogenetics41 including: * APL, t(15;17) * t(8;21) * inv(16) or t(16;16) A sample to evaluate patient cytogenetics will be sent at the time of diagnosis per standard clinical care and the absence of these cytogenetics must be confirmed by Day 8. If the cytogenetic analysis reveals that the patient harbors favorable risk cytogenetics, or if the cytogenetic results are not received prior to Day 8, the participant will be removed from the study. * Patients with acute bilineal/biphenotypic leukemia * Participants who have had chemotherapy or radiotherapy within 14 days prior to entering the study, except for hydroxyurea, 6-MP, and ATRA, as noted. * Participants who are receiving any other investigational agents. * Chemo-, hormono-, radio- or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug * Persistence of clinically relevant therapy related toxicity from previous anti-cancer therapy * Prior allogeneic bone marrow or organ transplantation * Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. * Current clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement (no lumbar puncture required, clinical assessment per investigator's judgment is sufficient). * Prior treatment with volasertib or another polo-like kinase inhibitor * A diagnosis of active Hepatitis B or C infection. A patient with a prior infection may participate, so long as the infection is not active at the time of study screening tests and according to investigator discretion. * Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome. Baseline QTc must be 470 msec or less, according to the Friderica correction method,42 calculated as the mean of 3 ECGs taken at the time of screening. * Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF \<50%, as measured by MUGA scan or echocardiogram). * Known hypersensitivity to the trial drugs or other contraindication to standard 7+3 induction chemotherapy. * Although not absolute
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Establishing The Maximum Tolerated Dose (MTD) | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Relapse Free Survival | 1 year | — |
| Rate of Overall Survival | 1 year | — |
| Rate of Complete Response | 2 years | — |
| Degree of change in the presence of subclones with Disease Response | 2 years | Measured by subclonal disease evolution, during treatment with volasertib and 7+3 |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 2 years | — |
| Rate of partial response | 2 years | — |
Countries
United States
Outcome results
None listed