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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT00301938

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 testing 7-hydroxystaurosporine, perifosine and pharmacological study in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
7-hydroxystaurosporine, perifosine and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Dec 2005to May 2012
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

  • 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
Show all 69Show fewer
  • 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:
  • -5q
  • 7q-
  • 9q-
  • 20q-
  • abn12p
  • +21
  • +8
  • t(6;9)
  • t(6;11)
  • t(11;19)
  • -7
  • -5
  • inv3/t(3;3)
  • abn11q23
  • abn17p
  • abn21q
  • t(9;22) refractory to imatinib mesylate
  • The following are considered adverse cytogenetic abnormalities for ALL:
  • t(9;22) refractory to imatinib mesylate
  • Hypodiploidy
  • t(4;11)
  • t(1;19)
  • Myelodysplastic Syndromes (MDS) meeting 1 of the following criteria:
  • Intermediate and high risk (i.e., International Prognostic Scoring System [IPSS] ≥ 1.5) MDS that is refractory or has progressed after treatment with azacitidine and/or decitabine
  • Intermediate and high risk (i.e., IPSS ≥ 1.5) MDS with a 5q- cytogenetic abnormality that is refractory or has progressed after treatment with lenalidomide, azacitidine, or decitabine
  • Intermediate 2 and high risk MDS without 5q- cytogenetic abnormality that is refractory or has progressed after azacitidine or decitabine
  • Original 5q must also be refractory to lenalidomide
  • Received OR ineligible for established curative regimens, including stem cell transplantation
  • No active CNS leukemia
  • ECOG performance status (PS) 0-2 OR Karnofsky PS ≥ 60%
  • Total or direct bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 times ULN
  • Creatinine ≤ 2 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • No hyperleukocytosis (i.e., WBC > 30,000/mm^3) (recent treatment with hydroxyurea to prevent impending leukostasis allowed provided there has been no dose increase for ≥ 1 week)
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to UCN-01 or perifosine
  • No intrinsic impaired organ function
  • No active, uncontrolled infection
  • Infection that is controlled with antibiotics allowed
  • No symptomatic cardiac disease
  • No active ischemia on EKG
  • LVEF ≥ 40% by echocardiogram or MUGA
  • Patients with a history of cardiac disease or mediastinal radiation should undergo testing of ventricular function
  • No poorly controlled diabetes mellitus
  • No psychiatric illness or social situation that would preclude giving informed consent or complying with study requirements
  • No HIV positivity
  • See Disease Characteristics
  • At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for carmustine or mitomycin C) and recovered
  • At least 4 weeks since prior radiotherapy and recovered
  • At least 4 weeks since prior autologous stem cell transplantation (SCT)
  • At least 90 days since prior allogeneic SCT
  • No evidence of graft vs host disease
  • At least 2 weeks since prior immunosuppressive therapy
  • No concurrent hematopoietic growth factors or biologic agents
  • No other concurrent investigational agents, chemotherapy, radiotherapy, or immunotherapy
  • No other concurrent anticancer therapy

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201-1595

Other trials in United States

About this study

Official title: A Phase 1 Study of UCN-01 in Combination With Perifosine in Patients With Relapsed and Refractory Acute Leukemias and High Risk MDS

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Define the maximum tolerated dose and recommended phase II dose of UCN-01 (7-hydroxystaurosporine) administered after perifosine in patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or high risk myelodysplastic disorders.

SECONDARY OBJECTIVES:

  1. Evaluate the safety and toxicity of UCN-01 administered after perifosine in these patients.

II. Evaluate the safety and toxicity of perifosine administered after UCN-01 in these patients.

III. Document responses in patients treated with this regimen. IV. Observe the pharmacokinetics of both perifosine and UCN-01 when administered in combination.

  1. Study the pharmacodynamics of perifosine alone, UCN-01 alone, and in combination in leukemic blast cells.

OUTLINE: This is a multicenter, dose-escalation study of 7-hydroxystaurosporine. The first patients enrolled in the study are assigned to arm 1. Once the maximum tolerated dose (MTD) is determined in arm 1, subsequent patients are enrolled in arm 2.

ARM 1: Patients 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 intravenously (IV) over 3 hours on day 4. Cohorts of 3-6 patients receive escalating doses of 7-hydroxystaurosporine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

ARM 2: Patients 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. In both groups, treatment repeats every 28 days for ≥ 2 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete remission (CR) or a CR with incomplete hematologic recovery receive 4 additional courses beyond documentation of CR. Patients who achieve a partial remission or hematologic improvement may continue treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days and then periodically thereafter.

Being tested
7-hydroxystaurosporine, perifosine, pharmacological study
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

  • 7-hydroxystaurosporineDrug

    Also called UCN-01

    Given IV

  • perifosineDrug

    Also called D21266, octadecylphosphopiperidine

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00301938
Study groupRoleWhat they receive
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.
Receives: Drug: 7-hydroxystaurosporine; Drug: perifosine; Other: pharmacological study
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.
Receives: Drug: 7-hydroxystaurosporine; Drug: perifosine; Other: pharmacological study

What is being measured

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

  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.

    Measured: Course 1 (first 28 days)

Secondary outcomes (5)

  1. Response rate, determined by improvement of blast cell count, degree of marrow infiltration by tumor cells, and improvement in peripheral blood count

    For patients with acute leukemias we will use revised International Working Group (IWG) response criteria as published by Cheson et al. For patients with MDS we will use IWG response assessment for MDS. 90% confidence interval (CI) will be provided.

    Measured: Baseline, at the end of course 1 (day 21-28), and any time that disease progression is suspected

  2. Progression free survival

    Estimated using the Kaplan-Meier method.

    Measured: The time between the study entry and the first date that relapse or progressive disease is objectively documented, or death from any cause occurs

  3. Disease specific survival and survival Rate

    Estimated using the Kaplan-Meier method.

    Measured: 1 year

  4. Overall survival

    Estimated using the Kaplan-Meier method.

    Measured: From time of enrollment onto this study to the time of death

  5. Pharmacokinetics and pharmacodynamics of both perifosine and 7-hydroxystaurosporine

    Descriptive statistics and confidence intervals will be provided for molecular endpoints of drugs action: total akt, phospho akt, total erk, phospho erk, p21 in peripheral blood and marrow. We will also dichotomize pharmacokinetic levels at the median, and estimate differences in response rates for high versus low levels, using Fisher's exact test at the one-sided 0.05 significance level.

    Measured: Baseline and at weeks 1, 5, and 9

Timeline

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

  1. First posted13 Mar 2006 (estimated)
  2. Study startDec 2005
  3. Primary completionMay 2012

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00301938
Sponsor's protocol ID
NCI-2009-00149
Other IDs
NCI-2009-00149, MSGCC-0507, NCI-7311, MSGCC-H-27229-0507, CDR0000465368, GCC 0507, 7311
Status last verified
Sep 2013
First submitted
9 Mar 2006
Last updated
30 Sep 2013
Results posted
No

Publications

  • 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.

    PubMed 23443507

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 7-hydroxystaurosporine, perifosine and pharmacological study in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Megakaryoblastic Leukemia (M7), run by National Cancer Institute (NCI) at 1 site 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 69 inclusion and 0 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: finished, as of the sponsor's last update on 30 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 of 7-hydroxystaurosporine administered after perifosine (time frame: Course 1 (first 28 days)). 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 NCT00301938, which also lists 1 linked publication.

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 30 Sep 2013.

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