Volasertib and Vincristine Sulfate Liposome in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT02861040|
Recruitment Status : Withdrawn
First Posted : August 10, 2016
Last Update Posted : December 15, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Adult Acute Lymphoblastic Leukemia Refractory Adult Acute Lymphoblastic Leukemia||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vincristine Sulfate Liposome Drug: Volasertib||Phase 1|
I. 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).
I. 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.
I. 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||August 2016|
|Estimated Primary Completion Date :||July 2018|
Experimental: Treatment (volasertib, vincristine sulfate liposome)
Patients 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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Vincristine Sulfate Liposome
Other Name: Marqibo
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to day 1 of cycle 2 ]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.
- Rate of complete remission (CR/Cri) [ Time Frame: After every 2 even number cycles during treatment then every 28 days up to 1 year during follow-up ]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.
- Duration of Remission (DOR) [ Time Frame: Up to 1 year from end of treatment ]DOR will be defined from the time, measured in months, of CR or CRi until disease progression.
- Minimal Residual Disease (MRD-negativity) rate [ Time Frame: Up to 1 year ]The rate of MRD-negativity will be assessed in bone marrow mononuclear cells by multi-color flow cytometry analysis.
- Progression Free Survival (PFS) [ Time Frame: Up to 1 year from end of treatment ]PFS will be defined as the time from treatment initiation until disease progression.
- Overall Survival (OS) [ Time Frame: Up to 1 year from end of treatment ]OS is defined as the time from treatment initiation until death from any cause.
- 30-day mortality rate [ Time Frame: Up to 30 days from the first dose of treatment ]Evaluated as the number of patients deceased within the first 30 days from the first dose of treatment.
- Mammalian target of rapamycin (mTOR) protein expression [ Time Frame: On cycle 1 day 1 and then 48 hours after 1st volasertib dose ]mTOR phosphoprotein expression levels before and after treatment with volasertib will be analyzed using blood samples which will determine whether protein levels are down-regulated after volasertib exposure.
- mTOR phosphoprotein expression levels and clinical response [ Time Frame: On cycle 1 day 1 and then 48 hours after 1st volasertib dose ]Assess statistical correlation of decreased mTOR phosphoprotein expression levels with clinical response to treatment with volasertib and VSLI.
- Interaction of Volasertib with VSLI in vivo [ Time Frame: At day 1 of cycle 1 ]Determine if volasertib acts synergistically to potentiate the bioavailability and distribution of VSLI using blood samples.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02861040
|United States, California|
|Palo Alto, California, United States, 94304|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Shira Dinner, MD||Northwestern University|