2nd Autologous Stem Cell Transplant in Patients With Persistent/Recurrent (AL) Amyloidosis

• Sponsor: Boston Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00075608
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 122
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having a 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.

PURPOSE: This phase II trial is studying how well autologous stem cell transplant works in treating patients with persistent or recurrent primary systemic (AL) amyloidosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Plasma Cell Neoplasm	Biological: filgrastim; Drug: melphalan; Procedure: autologous stem cell transplantation; Procedure: stem cell infusion	Phase 2

Detailed Description

OBJECTIVES:

• Determine the feasibility and tolerability of second autologous stem cell transplantation in patients with persistent or recurrent AL amyloidosis.

• Determine the response rate and durability of response in patients treated with this regimen.

• Determine immune reconstitution in patients treated with this regimen.

OUTLINE:

• Mobilization: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning before the initiation of stem cell collection and continuing until the day before the completion of stem cell collection.

• Preparative regimen: Patients receive high-dose melphalan IV over 20 minutes on days -3 and -2.

• Autologous stem cell transplantation: Autologous stem cells are reinfused on day 0.

Patients are followed at 6 months, 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 19 patients will be accrued for this study within 5-6 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Second Autologous Transplantation in AL Amyloidosis
• Study Start Date: Aug 1, 2001
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 2nd Stem Cell Transplant Mobilization with filgrastim autologous stem cell transplantation with melphalan conditioning stem cell infusion

Biological: filgrastim; 16mcg/kg IV daily beginning three days prior to stem cell collection through last day of stem cell collection; Other Names: G-CSF ; Drug: melphalan; 140-200 mcg/kg IV over two days; Other Names: alkeran ; Procedure: autologous stem cell transplantation; infusion of previously collected stem cells on Day 0; Procedure: stem cell infusion; infusion of previously collected stem cells on Day 0

Outcome Measures

Primary Outcome Measures

1. Feasibility and Tolerability [3 months after treatment and annually]

   Feasibility and tolerability will be evaluated based on participants completing second transplant with tolerable adverse events

2. Response and Durability of Response [3 months after treatment and annually]

   Response and durability of response will be based on hematologic Complete Response or Partial Response and date of relapse or death

3. Evaluate Immune Reconstitution [3 months after treatment and annually]

   Evaluate immune reconstitution based on time to engraftment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

DISEASE CHARACTERISTICS:

• Histologically confirmed AL amyloidosis

• Persistent or recurrent disease after 1 course of prior high-dose chemotherapy

• Previously treated with autologous stem cell transplantation

• Significant initial improvement in organ function after prior high-dose melphalan, defined by at least 1 of the following:

• Complete hematologic remission (e.g., absence of monoclonal spike by immunofixation in serum and urine AND less then 5% plasma cells in bone marrow with no clonal predominance) OR partial hematologic response (e.g., any decrease in serum or urine monoclonal protein OR decrease in bone marrow plasmacytosis)

• Greater than 50% reduction in proteinuria with preservation of creatinine clearance

• Greater than 50% reduction in alkaline phosphatase OR at least 2 cm decrease in liver size by physical exam

• Subjective neurologic improvement, as confirmed by neurologist

• Cardiac stabilization of disease confirmed by echocardiography defined as less than 2 mm increase in mean wall thickness and/or less than 20 g increase in left ventricular mass

• Improvement in performance status* NOTE: *This criteria alone does not constitute significant improvement in organ function

• Prior stem cell yield must have been ≥ 2 x 10^6 CD34+ cells/kg

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

• No chemotherapy after first transplantation

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• Southwest Oncology Group- 0-2

Life expectancy

• More than 6 months

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics

Renal

• See Disease Characteristics

Cardiovascular

• See Disease Characteristics

• Left ventricular ejection fraction ≥ 45% by multiple gated acquisition scan or echocardiogram

Pulmonary

• diffusing capacity of lung for carbon monoxide ≥ 50%

Exclusion Criteria:

• No myelodysplastic syndromes

• No abnormal bone marrow cytogenetics

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Acceptable toxicity from first transplantation, confirmed by the transplant team

• HIV negative

• No other concurrent malignancy except treated skin cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston Medical Center

Investigators

• Principal Investigator: Karen Quillen, MD, Boston Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Karen Quillen, Medical Director, Blood Bank, Boston Medical Center
• ClinicalTrials.gov Identifier: NCT00075608
• Other Study ID Numbers: CDR0000347379; H-22603
• First Posted: Jan 12, 2004
• Last Update Posted: Jan 27, 2017
• Last Verified: Dec 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Karen Quillen, Medical Director, Blood Bank, Boston Medical Center: primary systemic amyloidosis
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Amyloidosis; Melphalan

Study Results

Participant Flow

Recruitment Details	Participants were recruited from March 2003 through July 2008 through the transplant clinic and amyloid clinic.

Arm/Group Title	Second Transplant
Arm/Group Description	Participants underwent a second treatment with high dose chemotherapy and stem cell transplant
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Second Transplant
Arm/Group Description	Participants underwent a second treatment with high dose chemotherapy and stem cell transplant
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.25 (1)
Gender (Count of Participants)
Female	5 41.7%
Male	7 58.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Feasibility and Tolerability
Description	Feasibility and tolerability will be evaluated based on participants completing second transplant with tolerable adverse events
Time Frame	3 months after treatment and annually

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed due to study termination

Arm/Group Title	Second Transplant
Arm/Group Description	Participants underwent a second treatment with high dose chemotherapy and stem cell transplant
Measure Participants	0

2. Primary Outcome

Title	Response and Durability of Response
Description	Response and durability of response will be based on hematologic Complete Response or Partial Response and date of relapse or death
Time Frame	3 months after treatment and annually

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed due to study termination

Arm/Group Title	2nd SCT
Arm/Group Description	Mobilization with filgrastim Second autologous peripheral blood stem cell transplant with melphalan conditioning filgrastim: 16mcg/kg IV daily beginning three days prior to stem cell collection through last day of SCC melphalan: 140-200 mcg/kg IV over two days autologous bone marrow transplantation: infusion of previously collected stem cells on Day 0 peripheral blood stem cell transplantation: infusion of previously collected stem cells on Day 0
Measure Participants	0

3. Primary Outcome

Title	Evaluate Immune Reconstitution
Description	Evaluate immune reconstitution based on time to engraftment
Time Frame	3 months after treatment and annually

Outcome Measure Data

Analysis Population Description

No data were collected or analyzed due to study termination

Arm/Group Title	2nd SCT
Arm/Group Description	Mobilization with filgrastim Second autologous peripheral blood stem cell transplant with melphalan conditioning filgrastim: 16mcg/kg IV daily beginning three days prior to SCC through last day of SCC melphalan: 140-200 mcg/kg IV over two days autologous bone marrow transplantation: infusion of previously collected stem cells on Day 0 peripheral blood stem cell transplantation: infusion of previously collected stem cells on Day 0
Measure Participants	0

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Adverse events were assessed for up to 1 year.
Arm/Group Title	Second Transplant
Arm/Group Description	Participants who received a second transplant
All Cause Mortality
	Second Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Second Transplant
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Sepsis	2/12 (16.7%)	3
Cardiac disorders
hypotension	5/12 (41.7%)	5
arrhythmia	2/12 (16.7%)	2
Gastrointestinal disorders
nausea	3/12 (25%)	3
diarrhea	5/12 (41.7%)	5
General disorders
fatigue	8/12 (66.7%)	8
Infections and infestations
febrile neutropenia	8/12 (66.7%)	8
Renal and urinary disorders
Acute renal failure	2/12 (16.7%)	2
Other (Not Including Serious) Adverse Events
	Second Transplant
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
peripheral edema	2/12 (16.7%)	2
Gastrointestinal disorders
nausea	9/12 (75%)	13
diarrhea	5/12 (41.7%)	6
Investigations
hypocalcemia	2/12 (16.7%)	2
hypoalbuminemia	3/12 (25%)	3
Respiratory, thoracic and mediastinal disorders
dyspnea	3/12 (25%)	3

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.