Title

Using High-Dose Melphalan Plus Peripheral Stem Cell Transplantation to Treat Patients with Primary Systemic Amyloidosis (A Phase II Study)

Sponsor

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

Purpose of the Study

The purpose of this study was to evaluate the safety and effectiveness of high doses of the chemotherapy drug melphalan plus peripheral stem cell transplantation in treating patients who have primary systemic amyloidosis. Amyloidosis is a disease in which a certain type of protein is deposited in various organs, causing abnormal function. It can be caused by cancer or some other disease, or may have no known cause.

Results

The overall response rate in this study was 64 percent. Some patients (50 percent) experienced a major response (for example the patient had substantial improvement in organ function that had previously been impaired). The response among the other 14 percent was considered minor (for example, blood markers of disease showed improvement). Disease remained stable for five patients. One patient’s disease progressed (got worse). Three patients died of treatment-related causes. Researchers note that the risks are high in this treatment, but that the results show that it is a promising treatment and testing in larger phase III trials would be worthwhile with careful patient selection.

Conclusion

A successor study (E2A01 - A Phase I Study of Amifostine Followed By High-Dose Escalation of Melphalan with Stem Cell Reconstruction for Patients with Primary Systemic Amyloidosis) is currently active and a replacement study is being planned to open early in 2007.

Start Date

July 1998

Stop Date

May 2000

Number of Participating Patients

30

Eligibility Requirements

Patients were between 18 and 70 years old, with no previous amyloidosis. They had had no more than two previous courses of chemotherapy and at least four weeks had passed since they last received treatment with melphalan.

Study Design

Patients received daily injections of a substance that encourages the body to make blood (G-CSF) starting on day one. Peripheral stem cells were collected from the patient’s bloodstream through a tube inserted in a vein starting on day five. The stem cells, collected over about 10 days, were frozen. Within 30 days after stem cell collection, patients received high dose chemotherapy using the drug melphalan, and the stem cells were returned to the bloodstream through the tube in the vein. G-CSF was given daily until white blood cell counts return to safe levels.

Side Effects

Patients experienced serious side effects, including blood abnormalities which researchers expected to see with stem cell transplantation in this group of patients. Other serious side effects included diarrhea, nausea, mouth sores, anorexia, breathing and other problems. Three patients died from treatment-related heart and lung problems and multiple organ failure. The risk of infection with stem cell transplantation is high.

References

Gertz MA, Blood EA, Vesole DH, Abonour R, Lazarus HM, Greipp PR. A Multicenter Phase 2 Trial of Stem Cell Transplantation for Immunoglobulin Light-Chain Amyloidosis (E4A97): An Eastern Cooperative Oncology Group Study. Bone Marrow Transplant 2004 Jul;34(2):149-54. (E4A97) [Manuscript published 7/15/2004]

National Cancer Institute Patient Summary

http://www.cancer.gov/clinical_trials/view_clinicaltrials.aspx?version=patient&cdrid=66334

Reviewed by

Morie A. Gertz, MD, Mayo Clinic; Robert Gray, PhD, ECOG Statistician, Cheryl K. Rutledge, BSN, Indiana University Cancer Center; Mary Lou Smith, ECOG Patient Representative

Released May 5, 2006 (Revised July 11, 2006)