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Recurrent Adult Acute Lymphoblastic LeukemiaPhase 1NCT02861040

Volasertib and Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Vincristine Sulfate Liposome in people with Recurrent Adult Acute Lymphoblastic Leukemia and Refractory Adult Acute Lymphoblastic Leukemia, run by Northwestern University at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The main purpose of this investigational research study is to determine how safe and tolerable the study drug volasertib is in combination with liposomal vincristine (Marqibo; an FDA-approved drug) in patients with relapsed/refractory acute lymphoblastic leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Vincristine Sulfate Liposome
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Aug 2016to Jul 2018
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

  • Patients must have histologically confirmed diagnosis of Philadelphia-negative ALL by bone marrow biopsy or aspirate
  • Patients must have >= 5% blasts in the bone marrow
  • Patients must have refractory disease, disease relapse or progression after at least two prior systemic chemotherapy or immunotherapy regimens
  • Note: Exceptions may be made if a patient is deemed unfit for first-line salvage therapy by the treating physician; such cases should be clearly documented
  • Patients with a history of CNS (central nervous system) leukemia are eligible if they are not symptomatic from current CNS involvement; if there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly with intrathecal chemotherapy per the treating physician
  • Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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  • Patients must have adequate organ function within 14 days prior to registration, as defined below:
  • Total bilirubin =< 2 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/aspartate aminotransferase (ALT) (serum glutamic pyruvic transaminase [SPGT]) =< 3 x ULN
  • Creatinine =< 2 X ULN
  • Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months following completion of therapy; should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
  • FOCBP must have a negative pregnancy test within 14 days prior to registration on study
  • Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Who cannot join

  • Patients who have had chemotherapy, immunotherapy, or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events (=< grade 1 or patient's baseline) due to agents administered more than 2 weeks earlier are not eligible
  • Patients may not be receiving any other investigational agents within 7 days of registration
  • Patients may not be receiving any medications that are known to prolong QT interval unless reviewed and approved by the principal investigator (PI)
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to volasertib or VSLI are not eligible
  • Subject may not have had hematopoietic stem cell transplant (HSCT) meeting any of the following:
  • Is within 2 months of transplant from cycle 1 day 1 (C1D1)
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  • Has clinically significant graft-versus-host disease requiring treatment
  • Has >= grade 2 persistent non-hematological toxicity related to the transplant
  • Donor lymphocyte infusion (DLI) is not permitted < 30 days prior to study registration
  • Patients with >= grade 2 sensory or motor neuropathy are not eligible
  • Fridericia's corrected QT (QTcF) prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator (e.g., congenital long QT syndrome); the QTcF will be calculated as the mean of the 3 electrocardiograms (ECGs) taken at screening
  • NOTE: The formula used to calculate QTcF can be physician's choice, but it must be used consistently throughout the study
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
  • Ongoing or active infection requiring systemic treatment
  • Symptomatic congestive heart failure (>= class 3)
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would, in the investigator's opinion, limit compliance with study requirements
  • Known human immunodeficiency virus (HIV) infection
  • Known John Cunningham virus (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
  • Known clinically active hepatitis A, B, or C infections
  • NOTE: Patients with chronic hepatitis C virus (HCV) or hepatitis B virus (HBV) infection may enroll if other laboratory criteria are met; those with HBV surface antigen positivity may enroll only if maintained on appropriate suppressive antiviral therapy for the duration of enrollment in the trial
  • Second malignancy that requires active treatment
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Female patients who are pregnant or nursing are not eligible

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21231

  • Stanford University

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: A Phase I Clinical Trial Evaluating the Combination of Volasertib (BI-6727) With Vincristine Sulfate Liposomal Injections (VSLI) in Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia

The main purpose of this investigational research study is to determine how safe and tolerable the study drug volasertib is in combination with liposomal vincristine (Marqibo; an FDA-approved drug) in patients with relapsed/refractory acute lymphoblastic leukemia. While VSLI demonstrated an overall response rate of 35% in Acute Lymphoblastic Leukemia (ALL) patients that had failed to respond to or relapsed after chemotherapy, combining it with other agents may increase clinical benefit.

Volasertib inhibits proteins involved in the cell cycle that are increased in ALL. When volasertib inhibits these proteins ALL cells die. In the laboratory, volasertib has been shown to increase activity of vincristine against ALL cells. Therefore, we think the combination of volasertib and VSLI will be more effective against your leukemia than either drug used alone. This study will try to find out what effects, good and/or bad, this drug combination has on the patient and their cancer, and to find a dose that may be used in future studies.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of the combination of volasertib and vincristine sulfate liposomal injection (VSLI) in relapsed/refractory (RR) acute lymphoblastic leukemia (ALL).

SECONDARY OBJECTIVES:

  1. To determine the toxicity profile of volasertib and VSLI, rate of complete remission (with or without complete hematologic recovery; complete response [CR]/CR with incomplete hematologic recovery [CRi]), duration of remission (DOR), rate of minimal residual disease (MRD)-negativity, progression free survival (PFS), overall survival (OS), 30-day mortality rate.

TERTIARY OBJECTIVES:

  1. To determine if volasertib and polo-like kinase (plk)-inhibition down-regulates the mammalian target of rapamycin (mTOR) pathway.

II. Whether plk and mTOR inhibition correlates with clinical response to treatment. III. to determine if volasertib acts synergistically to potentiate the bioavailability and distribution of VSLI.

OUTLINE: This is a dose-escalation study of volasertib.

Patients receive volasertib intravenously (IV) over 1 hour on day 1 and vincristine sulfate liposome IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression, development of an inter-current illness that prevents further administration of treatment, unacceptable toxicity, patient decides to withdraw or treating investigator determines that the patient should be taken off treatment for any reason.

After completion of study, patients are followed up every 28 days for up to 1 year.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Vincristine Sulfate Liposome, Volasertib
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Vincristine Sulfate LiposomeDrug

    Also called Marqibo

    Given IV

  • VolasertibDrug

    Also called BI 6727, BI-6727, Polo-like Kinase 1 Inhibitor BI 6727

    Given IV

Study groups in NCT02861040
Study groupRoleWhat they receive
Treatment (volasertib, vincristine sulfate liposome)ExperimentalPatients receive volasertib IV over 1 hour on day 1 and vincristine sulfate liposome IV over 1 hour on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression, development of an inter-current illness that prevents further administration of treatment, unacceptable toxicity, patient decides to withdraw or treating investigator determines that the patient should be taken off treatment for any reason.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vincristine Sulfate Liposome; Drug: Volasertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD)

    Determine the MTD of volasertib and VSLI in RR ALL, the MTD will be defined as the highest dose level at which ≤ 1 Dose-Limiting Toxicity (DLT) occurs in 6 patients and will be assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

    Measured: Up to day 1 of cycle 2

Secondary outcomes (6)

  1. Rate of complete remission (CR/Cri)

    Evaluate the rate of complete remission (with or without complete hematologic recovery; CR/CRi). Rates will be based on the number and percentage of patients that achieve a CR/CRi. Response will be assessed by bone marrow biopsy and blood counts.

    Measured: After every 2 even number cycles during treatment then every 28 days up to 1 year during follow-up

  2. Duration of Remission (DOR)

    DOR will be defined from the time, measured in months, of CR or CRi until disease progression.

    Measured: Up to 1 year from end of treatment

  3. Minimal Residual Disease (MRD-negativity) rate

    The rate of MRD-negativity will be assessed in bone marrow mononuclear cells by multi-color flow cytometry analysis.

    Measured: Up to 1 year

  4. Progression Free Survival (PFS)

    PFS will be defined as the time from treatment initiation until disease progression.

    Measured: Up to 1 year from end of treatment

  5. Overall Survival (OS)

    OS is defined as the time from treatment initiation until death from any cause.

    Measured: Up to 1 year from end of treatment

  6. 30-day mortality rate

    Evaluated as the number of patients deceased within the first 30 days from the first dose of treatment.

    Measured: Up to 30 days from the first dose of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionJul 2018 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02861040
Sponsor's protocol ID
NU 16H06
Other IDs
STU00203179, NU 16H06, P30CA060553, NCI-2016-01036
Status last verified
Dec 2016
First submitted
2 Aug 2016
Last updated
15 Dec 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Vincristine Sulfate Liposome in people with Recurrent Adult Acute Lymphoblastic Leukemia and Refractory Adult Acute Lymphoblastic Leukemia, run by Northwestern University at 2 sites 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 16 inclusion and 25 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: withdrawn, as of the sponsor's last update on 15 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 was withdrawn before enrolling participants, so there are no results.

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?

Maximum Tolerated Dose (MTD) (time frame: Up to day 1 of cycle 2). 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 NCT02861040.

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 15 Dec 2016.

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