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

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00477971

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone Drug: filgrastim Drug: melphalan Procedure: autologous hematopoietic stem cell transplantation	Phase III

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Filgrastim Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Melphalan Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Hematologic response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Organ response to treatment [ Designated as safety issue: No ]
Patient-reported outcomes [ Designated as safety issue: No ]

Estimated Enrollment:	152
Study Start Date:	October 2005
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator 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.	Drug: dexamethasone Given orally Drug: melphalan Given IV or orally
Arm II: Experimental 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.	Drug: filgrastim No administration information given Drug: melphalan Given IV or orally Procedure: autologous hematopoietic stem cell transplantation Given on day 0

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 elevated 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00477971

Locations

United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Morie A. Gertz, MD	Mayo Clinic
Investigator:	Martha Q. Lacy, MD	Mayo Clinic
Investigator:	Angela Dispenzieri, MD	Mayo Clinic
Investigator:	Philip R. Greipp, MD	Mayo Clinic
Investigator:	Thomas E. Witzig, MD	Mayo Clinic
Investigator:	John A. Lust, MD, PhD	Mayo Clinic
Investigator:	S. V. Rajkumar, MD	Mayo Clinic
Investigator:	Steve Zeldenrust, MD	Mayo Clinic
Investigator:	Mark R. Litzow, MD	Mayo Clinic
Investigator:	Suzanne Hayman, MD	Mayo Clinic
Investigator:	Shaji K. Kumar, MD	Mayo Clinic
Investigator:	Stephen J. Russell, MD, PhD	Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000546745, MAYO-MC0482, MAYO-IRB-1691-05
Study First Received:	May 23, 2007
Last Updated:	January 7, 2009
ClinicalTrials.gov Identifier:	NCT00477971
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

primary systemic amyloidosis

Study placed in the following topic categories:

Dexamethasone
Melphalan
Metabolic Diseases
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias

Hemostatic Disorders
Multiple Myeloma
Amyloidosis
Hemorrhagic Disorders
Multiple myeloma
Metabolic disorder
Lymphoproliferative Disorders
Dexamethasone acetate
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents, Hormonal
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Immunosuppressive Agents

Hormones
Glucocorticoids
Pharmacologic Actions
Neoplasms
Autonomic Agents
Therapeutic Uses
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Alkylating Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009