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

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

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma and Plasma Cell Neoplasm
• Intervention / Treatment: Biological: anti-thymocyte globulin; Drug: melphalan

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Shaji K. Kumar, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: March 12, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: December 20, 2016
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Antilymphocyte Serum
• Other Study ID Numbers: CDR0000589032; P30CA015083 (U.S. NIH Grant/Contract); MC0687 (Other Identifier: Mayo Clinic Cancer Center); 06-005792 (Other Identifier: Mayo Clinic IRB)