Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

NCT ID: NCT00477971

Last Updated: 2016-05-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2014-12-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis.

PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

Detailed Description

OBJECTIVES:

Primary

• Compare hematologic response rate in patients with primary systemic amyloidosis treated with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs high-dose melphalan followed by autologous stem cell transplantation.
• Compare the toxicity of these regimens in these patients.

Secondary

• Compare the overall and progression-free survival of patients treated with these regimens.
• Compare the regression of organ involvement in patients treated with these regimens.
• Compare the duration of response in patients treated with these regimens.
• Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes in patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare the information-seeking behavior in patients treated with these regimens.

OUTLINE: This is a comprehensive cohort study comprising a randomized option and a nonrandomized option. Patients consenting to randomization are stratified by risk group (high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2 treatment arms. Patients not consenting to randomization choose their treatment arm.

• Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA, and nucleotide sequence analysis to determine VH and VL gene families and carrier status. Urine is collected at baseline and analyzed for light-chain protein levels by exclusion chromatography.

Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study treatment, and then every 6 months for up to 5 years.

After completion of study treatment, patients are followed every 6 months for up to 10 years.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Patients receive low-dose melphalan IV over 15-30 minutes on day

1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses.

Study treatment beyond one year is not allowed.

Group Type: ACTIVE_COMPARATOR

dexamethasone

Intervention Type: DRUG

Given orally

melphalan

Intervention Type: DRUG

Given IV or orally

Arm B

Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

No administration information given

melphalan

Intervention Type: DRUG

Given IV or orally

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Given on day 0

Interventions

filgrastim

No administration information given

Intervention Type: BIOLOGICAL

dexamethasone

Given orally

Intervention Type: DRUG

melphalan

Given IV or orally

Intervention Type: DRUG

autologous hematopoietic stem cell transplantation

Given on day 0

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed primary systemic amyloidosis

• Amyloid light-chain (AL) disease
• Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio
• The following amyloid syndromes* are allowed:

• Amyloid hepatomegaly
• Cardiomyopathy
• Proteinuria
• Peripheral or autonomic neuropathy
• Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication
• Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome
• No secondary or familial amyloidosis
• No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy
• No multiple myeloma with > 30% plasma cells in the bone marrow
• No amyloidosis manifested only by carpal tunnel syndrome or purpura

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 2.0 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 6 times ULN
• Creatinine ≤ 3.0 mg/dL
• No NYHA class IV heart disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No HIV positivity

PRIOR CONCURRENT THERAPY:

• Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for < 1 month

• Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician
• No concurrent participation in another clinical trial involving a pharmacologic agent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morie A. Gertz, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC0482

Identifier Type: OTHER

Identifier Source: secondary_id

1691-05

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-01329

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000546745

Identifier Type: -

Identifier Source: org_study_id