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

Multiple Myeloma and Plasma Cell Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00635024
• Other study ID #: CDR0000589032
• Secondary ID: P30CA015083MC068
• Status: Terminated
• Phase: Phase 2
• First received: March 12, 2008
• Last updated: August 19, 2011
• Start date: May 2008
• Est. completion date: November 2010

Study information

• Verified date: August 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: November 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Biological:
• anti-thymocyte globulin
2.5 mg/kg

Drug:
• melphalan
16 mg/m^2

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	4 months	No
Secondary	Overall Survival (OS)	OS was defined as the time from registration to death of any cause.	up to 2 years	No
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	up to 2 years	No
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.	up to 2 years	No
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)	every month during treatment, up to 12 months	Yes