Melphalan and Autologous Stem Cell Transplant Followed By Bortezomib and Dexamethasone in Treating Patients With Previously Untreated Systemic Amyloidosis

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00458822
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 96.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study in patients needing treatment for AL amyloidosis is to see how well treatment with IV melphalan works and then, if some clonal plasma cells are still present about 2 to 3 months after melphalan treatment, to see how well treatment with bortezomib and dexamethasone works to reduce the rest of the clonal plasma cell disease.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: bortezomib; Drug: dexamethasone	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risk-Adapted Intravenous Melphalan With Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients With Systemic Light-Chain (AL) Amyloidosis
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Mar 1, 2015
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All Patients All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis	Drug: bortezomib; Given IV; Drug: dexamethasone; Given orally

Outcome Measures

Primary Outcome Measures

1. Hematologic and Organ Response [2-3 months post transplant]

   patients will be assessed for hematologic response (the response of the clonal plasma cell disease). If the plasma cell disease persists, then they will receive 6 cycles of adjuvant therapy with bortezomib and dexamethasone; patients with peripheral neuropathy will receive dexamethasone alone because of the risk of neuropathy associated with bortezomib. Symptomatic organ involvement with amyloid as defined below. Patients must have symptomatic involvement of no more than 2 of the following 4 visceral organ-systems: kidneys, liver/GI, peripheral/autonomic nervous system, and heart.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed amyloidosis

• Diagnosed within the past 12 months

• Clonal plasma cell disorder, as demonstrated by any of the following:

• Presence of M-protein in serum and/or urine by immunofixation and/or serum free light chain assay

• Clonal population of plasma cells in the bone marrow based on kappa/lambda staining of a marrow biopsy

• Negative genetic testing for hereditary forms of amyloidosis

• No amyloid-specific syndrome (e.g., carpal tunnel syndrome or skin purpura) as the only evidence of disease

• Vascular amyloidosis only in a bone marrow biopsy specimen or in plasmacytoma is not indicative of systemic amyloidosis

• No advanced cardiac amyloidosis

• Must have symptomatic involvement of no more than 2 of the following visceral organ systems:

• Kidneys

• Liver/gastrointestinal

• Peripheral/autonomic nervous system

• Heart

• No persistent pleural effusions

• No clinically overt multiple myeloma with > 30% plasma cells in the bone marrow or lytic bone lesions

• Able to undergo autologous stem cell transplantation

PATIENT CHARACTERISTICS:

• SWOG performance status 0-3

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Bilirubin < 2.0 mg/dL

• Creatinine clearance < 51 mL/min allowed

• LVEF > 45% by echocardiogram

• No New York Heart Association class III-IV congestive heart failure

• No history of cardiac syncope

• No recurrent symptomatic arrhythmias

• No oxygen-dependent restrictive cardiomyopathy

• No myocardial infarction within the past 6 months

• Pulmonary diffusion capacity > 50% predicted by pulmonary function testing

• No uncontrolled infection

• No other active malignancy, except for any of the following:

• Adequately treated basal cell or squamous cell skin cancer

• In situ cervical cancer

• Adequately treated stage I cancer from which the patient is currently in complete remission

• Any other cancer from which the patient has been disease-free for 5 years

• No hypersensitivity to bortezomib, boron, or mannitol

• No HIV positivity

• No serious medical or psychiatric illness that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• At least 14 days since prior investigational drugs

• No prior therapy for monoclonal plasma disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Heather Landau, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00458822
• Other Study ID Numbers: 07-006; MSKCC-07006
• First Posted: Apr 11, 2007
• Last Update Posted: Aug 10, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: primary systemic amyloidosis
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Amyloidosis; Dexamethasone; Bortezomib

Study Results

Participant Flow

Arm/Group Title	All Patients
Arm/Group Description	All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis
Period Title: Overall Study
STARTED	40
COMPLETED	40
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	23 57.5%
Male	17 42.5%

Outcome Measures

1. Primary Outcome

Title	Hematologic and Organ Response
Description	patients will be assessed for hematologic response (the response of the clonal plasma cell disease). If the plasma cell disease persists, then they will receive 6 cycles of adjuvant therapy with bortezomib and dexamethasone; patients with peripheral neuropathy will receive dexamethasone alone because of the risk of neuropathy associated with bortezomib. Symptomatic organ involvement with amyloid as defined below. Patients must have symptomatic involvement of no more than 2 of the following 4 visceral organ-systems: kidneys, liver/GI, peripheral/autonomic nervous system, and heart.
Time Frame	2-3 months post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Patients
Arm/Group Description	All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis
Measure Participants	40
Complete Hematologic Response	11 27.5%
Partial Response	7 17.5%
Stable Disease	18 45%

Adverse Events

Arm/Group Title	All Patients
Arm/Group Description	All patients treated with Melphalan with Stem Cell Transplant and Adjuvant Bortezomib and Dexamethasone for Recently Diagnosed Untreated Patients with Systemic Light-Chain (AL) Amyloidosis
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	20/40 (50%)
Blood and lymphatic system disorders
Coagulation, other	2/40 (5%)	2
Platelets	4/40 (10%)	4
Cardiac disorders
Atrial fibrillation	1/40 (2.5%)	1
Cardiac Arrhythmia, other	1/40 (2.5%)	1
Cardiac General, other	6/40 (15%)	6
Hypotension	4/40 (10%)	5
Restrictive cardiomyopathy	1/40 (2.5%)	2
Supraventricular tachycardia	1/40 (2.5%)	1
Ventricular arrhythmia- Ventricular tachycardia	1/40 (2.5%)	1
Gastrointestinal disorders
Dehydration	1/40 (2.5%)	2
Hemorrhage, Upper GI NOS	1/40 (2.5%)	1
Nausea	1/40 (2.5%)	1
General disorders
Arthritis (non-septic)	1/40 (2.5%)	1
Conduction Abnormality NOS	1/40 (2.5%)	1
Death not associated with CTCAE term- Death NOS	3/40 (7.5%)	3
Febrile neutropenia	1/40 (2.5%)	1
Fever (in the absence of neutropenia)	1/40 (2.5%)	1
Hemorrhage/Bleeding, other	1/40 (2.5%)	1
Hypoxia	1/40 (2.5%)	1
Ocular/Visual - Other	1/40 (2.5%)	1
Infections and infestations
Neutrophil-Pneumonia (lung)	2/40 (5%)	2
Neutrophil-Up airway NOS	1/40 (2.5%)	1
Infection, other	5/40 (12.5%)	5
Metabolism and nutrition disorders
Sodium, low (hyponatremia)	1/40 (2.5%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/40 (2.5%)	1
Syncope (fainting)	4/40 (10%)	4
Vasovagal episode	2/40 (5%)	2
Renal and urinary disorders
Renal failure	3/40 (7.5%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	3/40 (7.5%)	4
Pulm/upper respiratory - Other	1/40 (2.5%)	1
Thrombosis/thrombus/embolism	2/40 (5%)	2
Skin and subcutaneous tissue disorders
Rash/desquamation	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	40/40 (100%)
Blood and lymphatic system disorders
ALT, SGPT	11/40 (27.5%)
AST, SGOT	6/40 (15%)
Hemoglobin	37/40 (92.5%)
Prothrombin Time international normalized ratio	10/40 (25%)
Leukocytes (total WBC)	38/40 (95%)
Lymphopenia	39/40 (97.5%)
Neutrophils/granulocytes	36/40 (90%)
Platelets	39/40 (97.5%)
Partial thromboplastin time	5/40 (12.5%)
Gastrointestinal disorders
Constipation	9/40 (22.5%)
Dehydration	2/40 (5%)
Diarrhea	3/40 (7.5%)
Distension/bloating, abdominal	3/40 (7.5%)
Nausea	4/40 (10%)
General disorders
Cholesterol,high(hypercholestremia)	6/40 (15%)
Cushingoid appearance	2/40 (5%)
Fatigue (asthenia, lethargy, malaise)	15/40 (37.5%)
Lipase	2/40 (5%)
Weight gain	2/40 (5%)
Infections and infestations
Infection, other	2/40 (5%)
Metabolism and nutrition disorders
Albumin, low (hypoalbuminemia)	31/40 (77.5%)
Alkaline phosphatase	9/40 (22.5%)
Bicarbonate, serum-low	5/40 (12.5%)
Bilirubin (hyperbilirubinemia)	6/40 (15%)
Creatinine	22/40 (55%)
Glucose, high (hyperglycemia)	27/40 (67.5%)
Glucose, low (hypoglycemia)	12/40 (30%)
Magnesium, high (hypermagnesemia)	5/40 (12.5%)
Magnesium, low (hypomagnesemia)	2/40 (5%)
Phosphate, low (hypophosphatemia)	18/40 (45%)
Potassium, high (hyperkalemia)	9/40 (22.5%)
Potassium, low (hypokalemia)	14/40 (35%)
Sodium, low (hyponatremia)	12/40 (30%)
Nervous system disorders
Neuropathy: sensory	10/40 (25%)
Pain - Neuralgia/peripheral nerve	7/40 (17.5%)
Syncope (fainting)	3/40 (7.5%)
Renal and urinary disorders
Renal failure	2/40 (5%)
Respiratory, thoracic and mediastinal disorders
Cough	3/40 (7.5%)
Dyspnea (shortness of breath)	4/40 (10%)
Skin and subcutaneous tissue disorders
Pruritus/itching	2/40 (5%)
Rash/desquamation	2/40 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.