A Treatment Guideline for High-Dose Melphalan with Autologous Hematopoietic Stem Cell Reconstitution for Primary Systemic Amyloidosis

Principal Investigator: Jeffrey V. Matous, MD

Protocol Number: RMBMT-08

Major Objectives

• Melphalan 100mg/m² on days –3 and –2

• Melphalan 140mg/m² on day –2

• Melphalan 100mg/m²

• Albumin infusions should be considered to keep serum albumin above 2.0
• Patients with known GI involvement should have platelet counts supported above 50,000/microliter if possible.
• Growth Factors should be avoided unless the attending physician feels the need outwiehgs the risk

Patient Selection

Inclusion Criteria:

1. Patients must have a history of a diagnosis of primary systemic amyloidosis, defined by both:
   1. Presence of paraprotein determined by immunoelectrophoresis/immunofixation of the serum or urine (no minimum values required), or by the serum free light chain assay. Both serum and urine studies must be evaluated at baseline and followed.
   2. Histologic documentation of organ involvement: at least one of the following are required for treatment:
      1. renal
      2. hepatic
      3. nerve,
      4. gastrointestinal or cardiac
2. Patients with known sensitivity to E. Coli derived proteins are excluded from this trial.
3. Patients must not have primary amyloidosis manifested only by carpal tunnel syndrome or purpura.
4. Patient must not have evidence of overt, symptomatic (BJH, 2003, NEJM 2004) multiple myeloma. Patients must not have a history of secondary, familial, or localized amyloidosis.
5. Patients must be 18 to 70 years of age.
6. ECOG performance status 0, 1, or 2
7. Patients must have the following laboratory values (within < 28 days prior to treatment):
   1. Granulocytes > 1000/mm³.
   2. Platelets > 100,000/mm³.
8. If total bilirubin is > 2.0 mg/dl, then direct bilirubin must be done and it must be < 2.0 mg/dl.
9. Serum creatinine < 2.0 mg/dL.
10. The following demonstrated by echocardiogram (Echocardiogram must be performed within 8 weeks prior to treatment. MUGA scans are NOT acceptable):
    1. Ejection fraction ≥ 40%
11. BNP and troponins will be drawn prior to transplant. If elevated, cariology will be consulted.

Exclusion Criteria:

1. Patients must not have New York Heart Association classification of II IV on appropriate therapy at the time of enrollment.
2. On pulmonary function tests performed within 8 weeks prior to treatment, patients must not have any of the following:
   • DLCO on pulmonary function of < 50%.
   • FVC < 60%.
   • FEV 1 < 55%
3. Patients must not have had any of the following prior therapies:
   • Melphalan therapy within 4 weeks prior to treatment.
   • Lifetime cumulative dose of melphalan > 150 m²
   • Note: Prior use of dexamethasone or interferon is allowed.
4. Patients must not be pregnant or breast feeding. Female patients of childbearing potential must have a negative pregnancy test within 14 days prior to treatment. These patients are excluded because the effects of this treatment on the fetus and young children are unknown.
5. Women of childbearing potential and sexually active mates must agree to use an effective method of contraception.
6. Patients must not have active infection