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CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Information source: Stanford University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

Intervention: liposomal cytarabine-daunorubicin CPX-351 (Drug); laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Suspended

Sponsored by: Bruno C. Medeiros

Official(s) and/or principal investigator(s):
Bruno de Medeiros, Principal Investigator, Affiliation: Stanford University Hospitals and Clinics

Summary

This phase II clinical trial studies how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-35, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Clinical Details

Official title: A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent

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

Primary outcome:

Incidence of mortality assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Incidence of mortality assessed using the CTCAE version 4.0

Incidence of serious adverse events as assessed by CTCAE version 4.0

Frequency of grade 3-5 adverse events as assessed by CTCAE version 4.0

Response rate (CR + CRi) following induction therapy using the European Leukemia Net classification for AML and the International Working Group guidelines for MDS

Secondary outcome:

Duration of remission following induction with CPX-351

Overall survival

Early induction mortality after first induction

Detailed description: PRIMARY OBJECTIVES: I. Determine the efficacy and safety profile of the use of CPX-351 in older patients (age 60 and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML. SECONDARY OBJECTIVES: I. Determine the duration of remission following induction therapy with CPX-351. II. Determine overall survival at 12 months. III. Determine the early induction mortality (at 60 days) following CPX-351 in this cohort following induction therapy. OUTLINE: INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive a second course of induction therapy. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 or after a second course of induction therapy proceed to consolidation therapy. SECOND INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Patients may receive a second course after 28-75 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 1 year.

Eligibility

Minimum age: 60 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Ability to understand and voluntarily give informed consent

- Age ≥ 60

- Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2

and high risk MDS by IPSS) along with one of the following:

- Patients with de novo or secondary MDS with progression/refractoriness after HMA

treatment who have not transformed to AML

- Patients with MDS and prior HMA treatment for MDS who transform to AML

- Patients with AML who are refractory/relapsed after HMA therapy for their AML

are eligible

- Life expectancy > 1 month

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Able to adhere to the study visit schedule and other protocol requirements

- Laboratory values fulfilling the following:

- Serum creatinine < 2. 0 mg/dL

- Serum total bilirubin ≤ 2. 5 mg/dL. Note, patients with Gilbert's syndrome may

have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their baseline total bilirubin.

- Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN

- Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography)

or MUGA scan

- Patients with second malignancies may be eligible at discretion of PI given acute

life threatening nature of untreated AML or higher risk MDS. Patients maintained on long-term non-chemotherapy treatment, e. g., hormonal therapy, are also eligible. Exclusion Criteria:

- Patients who have previously undergone allogeneic hematopoietic stem cell transplant

will be excluded from this study

- Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368

mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors). See appendix for anthracycline equivalence table.

- Acute promyelocytic leukemia [t(15;17)]

- Any serious medical condition, laboratory abnormality or psychiatric illness that

would prevent obtaining informed consent

- Patients who have had conventional intensive cytotoxic induction chemotherapy for

treatment of specifically MDS or AML are excluded.

- Patients who have not previously been treated with HMA therapy will be excluded

- Clinical evidence of active CNS leukemia

- Patients with evidence of uncontrolled current myocardial impairment (e. g. unstable

ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)

- Active and uncontrolled infection. Patients with an active infection receiving

treatment and hemodynamically stable for 48 hours may be entered into the study

- Known active uncontrolled HIV or hepatitis C infection

- Known hypersensitivity to cytarabine, daunorubicin or liposomal products

- Known history of Wilson's disease or other copper-related disorders

- Other medical or psychiatric illness or organ dysfunction or laboratory abnormality

which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

- Laboratory abnormalities:

- Serum creatinine ≥ 2. 0 mg/dL

- Serum total bilirubin > 2. 5 mg/dL. Note, patients with Gilbert's syndrome may

have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their baseline total bilirubin.

- Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN

Locations and Contacts

Stanford University Cancer Institute, Stanford, California 94305, United States
Additional Information

Starting date: February 2014
Last updated: August 6, 2015

Page last updated: August 20, 2015

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