Know Cancer

or
forgot password

Cyclosporine Modulation of Drug Resistance in Combination With Pravastatin, Mitoxantrone, and Etoposide for Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML): A Phase 1/2 Study


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Acute Myeloid Leukemia

Thank you

Trial Information

Cyclosporine Modulation of Drug Resistance in Combination With Pravastatin, Mitoxantrone, and Etoposide for Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML): A Phase 1/2 Study


PRIMARY OBJECTIVES:

I. Determine the maximum tolerated doses of mitoxantrone (mitoxantrone hydrochloride) and
etoposide in combination with pravastatin (pravastatin sodium) and cyclosporine.

SECONDARY OBJECTIVES:

I. Describe the complete remission (CR)/CR with incomplete peripheral blood count recovery
(CRi) rate after up to 2 cycles of induction therapy.

II. Describe the disease-free survival of patients that achieve CR/CRi. III. Estimate the
frequency and severity of regimen-associated toxicities, along with 28-day mortality after
start of study treatment.

OUTLINE: This is a phase I/II, dose-escalation study of etoposide and mitoxantrone
hydrochloride in combination with pravastatin sodium and cyclosporine.

Patients receive cyclosporine intravenously (IV) continuously on days 5-9. Patients also
receive pravastatin sodium orally (PO) every 6 hours on days 1-10, etoposide IV continuously
on days 5-9, and mitoxantrone hydrochloride IV continuously on days 5-9. Treatment repeats
for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients
achieving CR/CRi may receive 2 additional courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 month.


Inclusion Criteria:



- Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model

- Prior morphological diagnosis of AML according to the 2008 World Health Organization
(WHO) diagnostic criteria; patients with biphenotypic AML are eligible; patients with
acute promyelocytic leukemia with t(15;17)(q22;q12) and variants are ineligible

- Relapsed/persistent disease as defined by International Working Group criteria;
outside diagnostic material is acceptable as long as peripheral blood and/or bone
marrow slides are reviewed at the study institution; flow cytometric analysis of
peripheral blood and/or bone marrow should be performed according to institutional
practice guidelines

- Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT)
are eligible if relapse occurs > 180 days post-transplant provided symptoms of
graft-versus host disease are well controlled with stable use of immunosuppressive
agents

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, assessed at time
of registration

- Should be off any active therapy for AML with the exception of hydroxyurea or
low-dose cytarabine (=< 100 mg/m^2) for at least 14 days prior to study registration
unless patient has rapidly progressive disease, and all Grade 2-4 non-hematologic
toxicities must have resolved

- Bilirubin =< 2 x Institutional Upper Limit of Normal (IULN) unless elevation is
thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
(assessed within 7 days prior to registration)

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 x
IULN unless elevation is thought to be due to hepatic infiltration by AML (assessed
within 7 days prior to registration)

- Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to registration)

- Left ventricular ejection fraction >= 40%, assessed within 28 days prior to
registration, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography,
or other appropriate diagnostic modality, and no clinical evidence of congestive
heart failure; if the patient had anthracycline-based therapy since the most recent
cardiac assessment, cardiac evaluation should be repeated if there is clinical or
radiographical suspicion of cardiac dysfunction, or if the previous cardiac
assessment was abnormal

- Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) >
100,000/uL can be treated with leukapheresis prior to enrollment

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- Ability to understand and the willingness to sign a written informed consent
document; the consent can be obtained from a legally authorized representative if the
patient is unable to provide informed consent

Exclusion Criteria:

- Diagnosis of another malignancy, unless the patient was diagnosed at least 2 years
earlier and has been disease-free for at least 6 months following the completion of
curative intent therapy with the following exceptions:

- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible
for this study if definitive treatment for the condition has been completed

- Patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values are also
eligible for this study if hormonal therapy has been initiated or a radical
prostatectomy has been performed

- Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML)

- Known hypersensitivity to any study drug

- Human immunodeficiency virus (HIV)-positive patients are excluded if their cluster of
differentiation (CD)4 count is below 200 cells/uL or if they have active acquired
immune deficiency syndrome (AIDS)-related complications, as these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy

- Pregnancy or lactation; women of childbearing potential must undergo pregnancy test
within 7 days prior to registration

- Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting progressive signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment)

- Patients may not be receiving any other investigational agents

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated doses mitoxantrone hydrochloride and etoposide when combined with cyclosporine and pravastatin sodium

Outcome Description:

Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome Time Frame:

After completion of first 2 courses

Safety Issue:

Yes

Principal Investigator

Roland Walter

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2409.00

NCT ID:

NCT01342887

Start Date:

April 2011

Completion Date:

March 2012

Related Keywords:

  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Recurrent Adult Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109