Volasertib Combined With Induction Chemotherapy in Acute Myeloid Leukemia

NCT02905994 | Withdrawn Phase 1 DMC

• 1 other identifier: 16-299
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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

Conditions

AML

Keywords

Leukemia

Outcome Measures

Primary Outcomes (1)

• Establishing The Maximum Tolerated Dose (MTD)

  2 years

Secondary Outcomes (6)

• Rate of Complete Response

  2 years

• Rate of Relapse Free Survival

  1 year

• Rate of Overall Survival

  1 year

• Rate of partial response

  2 years

• Degree of change in the presence of subclones with Disease Response

  2 years

Study Arms (1)

Volasertib with chemotherapy

EXPERIMENTAL

Patients enrolled on this trial will receive induction chemotherapy with "7+3" * Cytarabine continuous infusion days 1-7 * Idarubicin IV bolus on days 1, 2, and 3. * Patients will receive Volasertib as an intravenous infusion over approximately 1 hour, according to dosing level, on day 8 * Patients will receive Standard Anti Fungal and Standard Antibiotic during induction * A bone marrow biopsy will be performed according to standard practice on day 14

Drug: Volasertib; Drug: Cytarabine; Drug: Idarubicin; Procedure: Bone Marrow Biopsy

Interventions

Volasertib DRUG

Polo-Like Kinase Inhibitor

Also known as: BI 6727

Volasertib with chemotherapy

Cytarabine DRUG

Standard chemotherapy at dosage and schedule for 7+3 induction

Also known as: Depocyt

Volasertib with chemotherapy

Idarubicin DRUG

Standard chemotherapy at dosage and schedule for 7+3 induction

Also known as: Idamycin

Volasertib with chemotherapy

Bone Marrow Biopsy PROCEDURE

Bone marrow biopsy assessments scheduled during induction to assess response

Volasertib with chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Boehringer Ingelheim: collaborator

Study Sites (2)

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia

Interventions

BI 6727; Cytarabine; Idarubicin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Amir T Fathi, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 19, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: May 4, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)