Multiple Myeloma, Plasma Cell Neoplasm
Conditions
Keywords
primary systemic amyloidosis
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.
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.
Interventions
BIOLOGICALfilgrastim
16mcg/kg IV daily beginning three days prior to stem cell collection through last day of stem cell collection
DRUGmelphalan
140-200 mcg/kg IV over two days
PROCEDUREautologous stem cell transplantation
infusion of previously collected stem cells on Day 0
PROCEDUREstem cell infusion
infusion of previously collected stem cells on Day 0
Sponsors
Boston Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Evaluate Immune Reconstitution | 3 months after treatment and annually | Evaluate immune reconstitution based on time to engraftment |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from March 2003 through July 2008 through the transplant clinic and amyloid clinic.
Participants by arm
| Arm | Count |
|---|---|
| Second Transplant Participants underwent a second treatment with high dose chemotherapy and stem cell transplant | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Second Transplant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 54.25 years STANDARD_DEVIATION 1 |
| Gender Female | 5 Participants |
| Gender Male | 7 Participants |
| Region of Enrollment United States | 12 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 12 / 12 |
Outcome results
Primary
Evaluate Immune Reconstitution
Evaluate immune reconstitution based on time to engraftment
Time frame: 3 months after treatment and annually
Population: No data were collected or analyzed due to study termination
Primary
Feasibility and Tolerability
Feasibility and tolerability will be evaluated based on participants completing second transplant with tolerable adverse events
Time frame: 3 months after treatment and annually
Population: No data were collected or analyzed due to study termination
Primary
Response and Durability of Response
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
Population: No data were collected or analyzed due to study termination