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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00635024
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: anti-thymocyte globulin; Drug: melphalan	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Thymoglobulin and Melphalan in Patients With Relapsed Multiple Myeloma
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Overall Survival (OS) [up to 2 years]

   OS was defined as the time from registration to death of any cause.

2. 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

3. 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.

4. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Study Chair: Shaji K. Kumar, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00635024
• Other Study ID Numbers: CDR0000589032; P30CA015083; MC0687; 06-005792
• First Posted: Mar 13, 2008
• Last Update Posted: Feb 10, 2017
• Last Verified: Aug 1, 2011

• Keywords provided by Mayo Clinic: refractory multiple myeloma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Melphalan; Antilymphocyte Serum

Study Results

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.

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Gender (Count of Participants)
Female	1 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%
Prior Stem Cell Transplant (participants) [Number]
Yes	1 100%
No	0 0%
Parameters of Hematologic Response (participants) [Number]
Yes	1 100%
No	0 0%
Parameters of Hematologic Response (participants) [Number]
Yes	1 100%
No	0 0%
Parameters of Hematologic Response (participants) [Number]
Yes	1 100%
No	0 0%
Parameters of Hematologic Response (participants) [Number]
Yes	1 100%
No	0 0%

Outcome Measures

1. Primary Outcome

Title	Hematological Response Rate Defined as the Number of Participants Who Achieve a Confirmed Response
Description	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

Outcome Measure Data

Analysis Population Description

One participant was evaluable for the primary endpoint.

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Measure Participants	1
Number [participants]	0 0%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from registration to death of any cause.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Measure Participants	1
Median (95% Confidence Interval) [months]	2.9

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Measure Participants	1
Median (95% Confidence Interval) [months]	2.9

4. Secondary Outcome

Title	Duration of Response (DOR)
Description	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

Outcome Measure Data

Analysis Population Description

All patients are non-evaluable - no patients responded to treatment.

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Measure Participants	0

5. Secondary Outcome

Title	Number of Participants With Severe Non-hematological Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
Measure Participants	1
Yes	1 100%
No	0 0%

Adverse Events

Arm/Group Title	Anti-thymocyte Globulin/Melphalan
Arm/Group Description	Anti-thymocyte Globulin (2.5 mg/Kg)and Melphalan (16 mg/m^2)
All Cause Mortality
	Anti-thymocyte Globulin/Melphalan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Anti-thymocyte Globulin/Melphalan
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Anti-thymocyte Globulin/Melphalan
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Anemia	1/1 (100%)	1
Immune system disorders
Hypersensitivity	1/1 (100%)	1
Infections and infestations
Opportunistic Infection	1/1 (100%)	1
Investigations
Leukopenia	1/1 (100%)	1
Neutrophil Count Decreased	1/1 (100%)	1
Platelet Count Decreased	1/1 (100%)	2

Limitations/Caveats

After 1 patient was recruited, this trial temporarily closed to allow the first dose of Anti-thymocyte Globulin to be split over two days. Before the modification was written, it was decided to permanently close this study due to competing trials.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.