Title

Comparing Combination Chemotherapy To Combination Chemotherapy Plus a Drug Called PSC 833 In Patients With Poor-Risk Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome (A Phase III Trial)

Sponsor

Eastern Cooperative Oncology Group through the NCI-sponsored Cancer Cooperative Group Program

Purpose of the Study

To find out whether the addition of PSC-833 to a standard chemotherapy drug combination is beneficial in treating patients with poor-risk acute myelogenous leukemia (AML) that has returned or is resistant to treatment and in patients with high-risk myelodysplastic syndrome (MDS). Laboratory studies have shown that PSC-833 may decrease the resistance of leukemia cells to combination chemotherapy, and enhance the effectiveness of treatment.

Results

The study did not show improved anti-leukemia effects in combination chemotherapy plus PSC-833 compared with combination chemotherapy alone in patients with poor-risk AML or high-risk MDS.

Conclusion

No other studies are planned with the drug PSC833 in the treatment of acute myeloid leukemia. However, to further understand the reasons why AML is resistant to many drugs and to determine whether a different compound may be more useful in this regard, ECOG is conducting another study, E3999, using the multidrug resistance modulator Zosquidar plus chemotherapy, as a follow-up. The data from E3999 are currently being analyzed.

Start Date

August 1997

Stop Date

May 1999

Number of Participating Patients

144

Eligibility Requirements

Patients were between 15-70 years old and had AML which did not respond to prior chemotherapy or which had recurred after an initial response to treatment. High-risk MDS patients were also eligible for the study. Their disease must not have affected their central nervous system. Patients must not have received chemotherapy or radiation therapy during the four weeks before entering the study.

Study Design

Patients were placed randomly in one of two groups. Patients in group one received three chemotherapy drugs, mitoxantrone, etoposide, and cytarabine, infused (injected through a vein) once a day for five days, plus a continual dose of PSC 833 through a vein for the same five days. Patients in the second group received an injection of only the three chemotherapy drugs once a day for five days. All patients received follow-up evaluations.

Side Effects

The most frequent side effects during treatment were nausea, vomiting, diarrhea, mouth ulcers, liver chemistry problems and infections. PSC-833 sometimes causes loss of coordination and unsteadiness in walking.

References

Greenberg PL, Lee S, Advani R, Tallman MS, Sikic BI, Letendre L, Dugan K, Lum B, Chin D, Dewald G, Paietta EM, Bennett JM, Rowe JM. Mitoxantrone, Etoposide and Cytarabine with or without Valspodar in Patients with Relapsed or Refractory Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome: A Phase III Trial (E2995). J Clin Oncol 2004 Mar 15;22(6):1078-86. (E2995) [Manuscript published 3/15/2004]

National Cancer Institute Patient Summary

http://www.cancer.gov/clinical_trials/view_clinicaltrials.aspx?version=patient&cdrid=65701

Reviewed by

Peter Greenberg, MD, Stanford University; Robert Catalano, PharmD, ECOG Regulatory Officer; Cheryl Rutledge, BSN, Indiana University Cancer Center

Released August 18, 2005 (Revised July 21, 2006)