Volasertib and Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
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
4 other identifiers
interventional
N/A
1 country
2
Brief 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. 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.
Trial Health
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2 active sites
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2016
CompletedFirst Submitted
Initial submission to the registry
August 2, 2016
CompletedFirst Posted
Study publicly available on registry
August 10, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2018
CompletedDecember 15, 2016
December 1, 2016
1.9 years
August 2, 2016
December 13, 2016
Conditions
Outcome Measures
Primary Outcomes (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.
Up to day 1 of cycle 2
Secondary Outcomes (6)
Rate of complete remission (CR/Cri)
After every 2 even number cycles during treatment then every 28 days up to 1 year during follow-up
Duration of Remission (DOR)
Up to 1 year from end of treatment
Minimal Residual Disease (MRD-negativity) rate
Up to 1 year
Progression Free Survival (PFS)
Up to 1 year from end of treatment
Overall Survival (OS)
Up to 1 year from end of treatment
- +1 more secondary outcomes
Other Outcomes (3)
Mammalian target of rapamycin (mTOR) protein expression
On cycle 1 day 1 and then 48 hours after 1st volasertib dose
mTOR phosphoprotein expression levels and clinical response
On cycle 1 day 1 and then 48 hours after 1st volasertib dose
Interaction of Volasertib with VSLI in vivo
At day 1 of cycle 1
Study Arms (1)
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.
Interventions
Correlative studies
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- 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
- +1 more criteria
You may not qualify if:
- 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)
- 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)
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Comprehensive Cancer Networkcollaborator
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Stanford University
Palo Alto, California, 94304, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21231, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shira Dinner, MD
Northwestern University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 2, 2016
First Posted
August 10, 2016
Study Start
August 1, 2016
Primary Completion
July 1, 2018
Last Updated
December 15, 2016
Record last verified: 2016-12