Anti-thymocyte Globulin and Melphalan in Treating Patients With Relapsed Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of Thymoglobulin and Melphalan in Patients With Relapsed Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: melphalan


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-thymocyte Globulin/Melphalan<br>Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2) | Biological: anti-thymocyte globulin<br>* 2.5 mg/kg<br>Drug: melphalan<br>* 16 mg/m^2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time from registration to death of any cause. | up to 2 years | 
| 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 | up to 2 years | 
| 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. | up to 2 years | 
| 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) | every month during treatment, up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma