7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes
A Phase 1 Study of UCN-01 in Combination With Perifosine in Patients With Relapsed and Refractory Acute Leukemias and High Risk MDS
7 other identifiers
interventional
30
1 country
1
Brief Summary
This phase I trial is studying the side effects and best dose of 7-hydroxystaurosporine when given together with perifosine in treating patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. 7-Hydroxystaurosporine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as perifosine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving 7-hydroxystaurosporine together with perifosine may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2005
CompletedFirst Submitted
Initial submission to the registry
March 9, 2006
CompletedFirst Posted
Study publicly available on registry
March 13, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2012
CompletedSeptember 30, 2013
September 1, 2013
6.4 years
March 9, 2006
September 27, 2013
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose of 7-hydroxystaurosporine administered after perifosine
Evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The highest dose with none or one DLT observed in six patients will be declared as MTD. To ensure the toxicity at the MTD is acceptable, additional 6 patients will be accrued at the MTD.
Course 1 (first 28 days)
Secondary Outcomes (5)
Response rate, determined by improvement of blast cell count, degree of marrow infiltration by tumor cells, and improvement in peripheral blood count
Baseline, at the end of course 1 (day 21-28), and any time that disease progression is suspected
Progression free survival
The time between the study entry and the first date that relapse or progressive disease is objectively documented, or death from any cause occurs
Disease specific survival and survival Rate
1 year
Overall survival
From time of enrollment onto this study to the time of death
Pharmacokinetics and pharmacodynamics of both perifosine and 7-hydroxystaurosporine
Baseline and at weeks 1, 5, and 9
Study Arms (2)
Arm I (enzyme inhibitor, chemotherapy)
EXPERIMENTALPatients receive a loading dose of oral perifosine every 6 hours on day 1 followed by a maintenance dose once daily on days 2-28 of course 1 and then once daily on days 1-28 in all subsequent courses. Patients also receive 7-hydroxystaurosporine IV over 3 hours on day 4. Cohorts of 3-6 patients receive escalating doses of 7-hydroxystaurosporine until the MTD is determined.
Arm 2 (enzyme inhibitor, chemotherapy)
EXPERIMENTALPatients receive 7-hydroxystaurosporine IV over 3 hours on day 1 at the MTD determined in group I. Patients also receive oral perifosine as a loading dose every 6 hours on day 4 followed by a maintenance dose once daily on days 5-28 of course 1 and then once daily on days 1-28 in all subsequent courses.
Interventions
Given IV
Given orally
Correlative studies
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed hematologic malignancy of 1 of the following types:
- Relapsed or refractory acute myelogenous leukemia (AML)
- Patients with acute promyelocytic leukemia t(15;17) are eligible provided they failed a prior tretinoin and arsenic-containing regimen
- Patients should be either refractory to both agents (absence of durable hematologic response) OR relapsed after a complete response duration of \< 6 months
- Relapsed or refractory pre-B-cell or T-cell acute lymphoblastic leukemia (ALL)
- Chronic myelogenous leukemia (CML) in accelerated or blastic phase that is refractory to imatinib mesylate
- Must have evidence of disease progression despite continued treatment with imatinib mesylate
- AML arising in the setting of underlying myelodysplastic syndromes (MDS) and/or myeloproliferative disorders (MPD)
- Secondary or therapy-related AML
- De novo AML or pre-B-cell or T-cell ALL in adults \> 60 years of age with poor-risk features, such as complex (≥ 3) or adverse cytogenetics
- The following are considered adverse cytogenetic abnormalities for AML:
- abn12p
- +21
- t(6;9)
- t(6;11)
- +47 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201-1595, United States
Related Publications (1)
Gojo I, Perl A, Luger S, Baer MR, Norsworthy KJ, Bauer KS, Tidwell M, Fleckinger S, Carroll M, Sausville EA. Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome. Invest New Drugs. 2013 Oct;31(5):1217-27. doi: 10.1007/s10637-013-9937-8. Epub 2013 Feb 27.
PMID: 23443507DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ivana Gojo
University of Maryland Greenebaum Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 9, 2006
First Posted
March 13, 2006
Study Start
December 1, 2005
Primary Completion
May 1, 2012
Last Updated
September 30, 2013
Record last verified: 2013-09