Multiple Myeloma and Plasma Cell Neoplasm
Conditions
Keywords
refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Biological therapies, such as anti-thymocyte globulin, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Anti-thymocyte globulin may also make cancer cells more sensitive to melphalan. Giving anti-thymocyte globulin together with melphalan may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving anti-thymocyte globulin together with melphalan works in treating patients with relapsed multiple myeloma.
Detailed description
OBJECTIVES: Primary \* To evaluate the hematological response rate of anti-thymocyte globulin given in combination with melphalan in patients with relapsed multiple myeloma. Secondary * To assess the toxicity and tolerability of this combination in these patients. * To assess time to disease progression in patients treated with these drugs. * To assess survival of patients treated with these drugs. OUTLINE: Patients receive anti-thymocyte globulin IV over 6 hours and melphalan IV on day 1. Treatment repeats every 28 days for 6 courses. Patients then receive melphalan alone as above for another 6 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.
Interventions
BIOLOGICALanti-thymocyte globulin
2.5 mg/kg
DRUGmelphalan
16 mg/m\^2
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of multiple myeloma \- Relapsed disease * Must not be a candidate for stem cell transplantation, has refused transplantation, or has had stem cells collected previously * Measurable disease, defined by ≥ 1 of the following: * Serum monoclonal protein ≥ 1.0 g by protein electrophoresis * More than 200 mg of monoclonal protein in the urine on 24 hour electrophoresis * Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease) PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-3 * Absolute neutrophil count ≥ 1,000/μL * Platelet count ≥ 75,000/μL * Hemoglobin ≥ 8.0 g/dL * CD4 \> 100/μL * Creatinine ≤ 3 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active malignancy with the exception of nonmelanoma skin cancer or in situ cervical or breast cancer * No uncontrolled infection * No other co-morbidity that would interfere with patient's ability to participate in trial PRIOR CONCURRENT THERAPY: * No limit to prior therapy * At least 4 weeks since prior melphalan or other myelosuppressive agents * At least 2 weeks since prior non-myelosuppressive agents (e.g., thalidomide or high-dose corticosteroids) * No concurrent high-dose corticosteroids * Concurrent chronic steroids (maximum dose 20 mg/day prednisone equivalent) allowed if they are being given for disorders other than amyloid (e.g., adrenal insufficiency or rheumatoid arthritis) * Concurrent continuation of low level/stable steroid doses for replacement or inhalation therapy allowed * Concurrent bisphosphonates allowed * No concurrent immunosuppressive medications such as cyclosporine * No other concurrent investigational treatment * No concurrent cytotoxic chemotherapy or external-beam radiotherapy\> * No other concurrent systemic anti-neoplastic therapy including, but not limited to, immunotherapy, hormonal therapy, or monoclonal antibody therapy * No concurrent prophylactic hematopoietic growth factors (unless for treatment of an established cytopenia)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematological Response Rate Defined as the Number of Participants Who Achieve a Confirmed Response | 4 months | Response that was confirmed on 2 consecutive evaluations during the first 4 months of treatment. Complete Response(CR): Disappearance of M-protein from serum and urine, normalization of Free Light Chain (FLC) ratio and \<5% plasma cells in bone marrow. Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<100mg per 24hours. Partial Response(PR): \>=50% reduction in serum M-component and/or Urine M-Component \>=90% reduction or \<200mg per 24hours; or \>=50% decrease in difference between involved and uninvolved FLC levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 2 years | OS was defined as the time from registration to death of any cause. |
| Progression-free Survival (PFS) | up to 2 years | PFS was defined as the time from registration to progression or death due to any cause. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in: * Serum M-component (absolute increase \>= 0.5g/dl) * Urine M-component (absolute increase \>= 200mg/24hour * Difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl) * Bone marrow plasma cell percentage (absolute increase of \>=10%) * Definite development of new bone lesion or soft tissue plasmacytomas |
| Duration of Response (DOR) | up to 2 years | DOR was calculated from the documentation of response (CR, VGPR or PR) until the date of progression in the subset of patients who responded. |
| Number of Participants With Severe Non-hematological Adverse Events | every month during treatment, up to 12 months | Severe non-hematologic adverse events were defined as adverse events grade 3 or higher, regardless of attribution to study drug. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0) |
Countries
United States
Participant flow
Recruitment details
One (1) patient was recruited from May 2008 to September 2008 at Mayo Clinic. This trial was permanently closed in March 2009 due to competing trials.
Participants by arm
| Arm | Count |
|---|---|
| Anti-thymocyte Globulin/Melphalan Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m\^2) | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Anti-thymocyte Globulin/Melphalan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Gender Female | 1 Participants |
| Gender Male | 0 Participants |
| Parameters of Hematologic Response No | 0 participants |
| Parameters of Hematologic Response Yes | 1 participants |
| Prior Stem Cell Transplant No | 0 participants |
| Prior Stem Cell Transplant Yes | 1 participants |
| Region of Enrollment United States | 1 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Hematological Response Rate Defined as the Number of Participants Who Achieve a Confirmed Response
Response that was confirmed on 2 consecutive evaluations during the first 4 months of treatment. Complete Response(CR): Disappearance of M-protein from serum and urine, normalization of Free Light Chain (FLC) ratio and \<5% plasma cells in bone marrow. Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<100mg per 24hours. Partial Response(PR): \>=50% reduction in serum M-component and/or Urine M-Component \>=90% reduction or \<200mg per 24hours; or \>=50% decrease in difference between involved and uninvolved FLC levels.
Time frame: 4 months
Population: One participant was evaluable for the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anti-thymocyte Globulin/Melphalan | Hematological Response Rate Defined as the Number of Participants Who Achieve a Confirmed Response | 0 participants |
Secondary
Duration of Response (DOR)
DOR was calculated from the documentation of response (CR, VGPR or PR) until the date of progression in the subset of patients who responded.
Time frame: up to 2 years
Population: All patients are non-evaluable - no patients responded to treatment.
Secondary
Number of Participants With Severe Non-hematological Adverse Events
Severe non-hematologic adverse events were defined as adverse events grade 3 or higher, regardless of attribution to study drug. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0)
Time frame: every month during treatment, up to 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Anti-thymocyte Globulin/Melphalan | Number of Participants With Severe Non-hematological Adverse Events | Yes | 1 participants |
| Anti-thymocyte Globulin/Melphalan | Number of Participants With Severe Non-hematological Adverse Events | No | 0 participants |
Secondary
Overall Survival (OS)
OS was defined as the time from registration to death of any cause.
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thymocyte Globulin/Melphalan | Overall Survival (OS) | 2.9 months |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from registration to progression or death due to any cause. Progression was defined as any one or more of the following: An increase of 25% from lowest confirmed response in: * Serum M-component (absolute increase \>= 0.5g/dl) * Urine M-component (absolute increase \>= 200mg/24hour * Difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl) * Bone marrow plasma cell percentage (absolute increase of \>=10%) * Definite development of new bone lesion or soft tissue plasmacytomas
Time frame: up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anti-thymocyte Globulin/Melphalan | Progression-free Survival (PFS) | 2.9 months |