Clinical Trial: Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: 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

Brief Summary: This phase I/II trial studies the side effects and best dose of etoposide and mitoxantrone hydrochloride when given together with cyclosporine and pravastatin sodium and to see how well they work in treating patients with relapsed or refractory acute myeloid leukemia (AML). Cyclosporine may inhibit efflux of cancer drugs out of cancer cells and may thereby improve chemotherapy treatment for AML. Pravastatin sodium may stop the growth of cancer cells by blocking some of the nutrients needed for cell growth. Drugs used in chemotherapy, such as etoposide and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving cyclosporine together with pravastatin sodium, etoposide, and mitoxantrone hydrochloride may kill more cancer cells

Detailed Summary:

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.


Sponsor: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Current Primary Outcome:

  • Maximum tolerated doses mitoxantrone hydrochloride and etoposide when combined with cyclosporine and pravastatin sodium [ Time Frame: After completion of first 2 courses ]
    Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
  • CR/CRi rate [ Time Frame: After completion of first 2 courses ]
    Categorized according to criteria recommended by an International Working Group.


Original Primary Outcome:

  • Maximum tolerated doses [ Time Frame: After completion of first 2 courses (induction therapy), an expected average of 2 months ]
    Determine the maximum tolerated doses of mitoxantrone and etoposide in combination with pravastatin and cyclosporine (Phase I only). Measures the number of patients with dose-limiting toxicities
  • CR/CRi rate [ Time Frame: After 1st and 2nd induction course, after an expected average of 1 and 2 months ]
    Describe the complete remission (CR)/CR with incomplete peripheral blood count recovery (CRi) rate after up to 2 cycles of induction therapy (Phase I and II).


Current Secondary Outcome:

  • Disease-free survival of patients that achieve CR/CRi [ Time Frame: Up to 4.5 years ]
  • Frequency and severity of regimen-associated toxicities [ Time Frame: Up to 1 month after completion of study treatment ]
  • Treatment-related mortality score [ Time Frame: At 28 days ]


Original Secondary Outcome:

  • Disease-free survival of patients that achieve CR/CRi [ Time Frame: Up to 4.5 years ]
  • Frequency and severity of regimen-associated toxicities [ Time Frame: Up to 1 month after completion of study treatment ]
  • Mortality [ Time Frame: At 28 days ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: April 22, 2011
Date Started: April 2011
Date Completion:
Last Updated: June 18, 2012
Last Verified: June 2012