Melphalan, Peripheral Stem Cell Transplantation, and Interleukin-2 Followed by Interferon Alfa in Treating Patients With Advanced Multiple Myeloma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00006244
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Location: 1
• Arm: 1
• Duration (Months): 194
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies the effectiveness of melphalan, peripheral stem cell transplantation, and interleukin-2 followed by interferon alfa in treating patients who have advanced multiple myeloma (MM). Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Interleukin-2 (IL2) may stimulate a person's white blood cells to kill multiple myeloma cells. Interferon alfa may interfere with the growth of cancer cells

Condition or Disease	Intervention/Treatment	Phase
Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Drug: melphalan; Biological: recombinant interferon alfa; Biological: aldesleukin; Procedure: in vitro-treated peripheral blood stem cell transplantation	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate initial response to therapy, time to disease progression, and overall survival in MM patients treated with melphalan, IL2- incubated peripheral blood stem cells, and sequential IL2.

SECONDARY OBJECTIVES:

1. Evaluate grade 3-4 toxicities encountered by younger (< 56 years old) and older (>56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.

OUTLINE:

Patients receive melphalan intravenously (IV) over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa subcutaneously (SC) 3 times a week in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immunotherapy for Autologous/Syngeneic Peripheral Blood Stem Cell (PBSC) Transplant Patients as Treatment for Advanced Multiple Myeloma
• Study Start Date: Feb 1, 2000
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (immunotherapy) Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity.

Drug: melphalan; Given IV; Other Names: Alkeran CB-3025 L-PAM L-phenylalanine mustard L-Sarcolysin ; Biological: recombinant interferon alfa; Given SC; Other Names: Alferon N alpha interferon IFN-A Intron A Roferon-A ; Biological: aldesleukin; Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion; Other Names: IL-2 Proleukin recombinant human interleukin-2 recombinant interleukin-2 ; Procedure: in vitro-treated peripheral blood stem cell transplantation; Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion; Other Names: in vitro-treated PBPC transplantation in vitro-treated PBSC in vitro-treated peripheral blood progenitor cell transplantation PBPC transplantation, in vitro-treated peripheral blood progenitor cell transplantation, in vitro-treated

Outcome Measures

Primary Outcome Measures

1. Overall Survival [12.9 Median Years]

   Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance.

2. Initial Response to Therapy [Evaluated at Day +84-90 Post-Transplant]

   Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease)

3. Time to Disease Progression [12.9 years (median)]

4. Proportion of Patients Alive and in Remission [12.9 Median Years]

Secondary Outcome Measures

1. Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity [First 100 days post-transplant]

   Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by younger (< 56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.

2. Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity [First 100 days post-transplant]

   Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by older (≥56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must be less than 70 years old

• Patients with advanced Multiple Myeloma that meet the eligibility requirements for mobilization/debulking with Cytoxan/VP-16/G-CSF, Cytoxan/Taxol/G-CSF, or Cytoxan/G-CSF (according to protocol 506.03); if clinically indicated a lower dose of cytoxan than 4g/m2 may be used for mobilization based on the attending's discretion; also, if the patients had previously collected PBSC of sufficient number in the past and meet the other eligibility requirements, they may be entered on this study after approval by the PI

• Patients with advanced Multiple Myeloma that have an identical syngeneic twin for donation of PBSCs

• Patients have advanced Multiple Myeloma if they were diagnosed initially with stage II or III disease or had stage I disease that progressed after initial therapy or failed to respond to therapy

• Syngeneic Donor Inclusion:

• Donor and patient have adequate documentation that donor and recipient are syngeneic; including ABO typing, HLA typing and VNTR studies

• Donor > 20 kg

• Donor meets eligibility to donate according to Standard Practice Guidelines

Exclusion Criteria:

• Patient's age >= 70

• Karnofsky score less than 80

• A left ventricular ejection fraction less than 50%; Patients with congestive heart disease, history of myocardial infarction (MI), coronary artery disease or any arrhythmia history

• Total bilirubin > 1.5 mg/ml (unless history of Gilbert's disease)

• Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2 x upper limit of normal

• Estimated creatinine clearance < 60 ml/min or creatinine serum > 2.0 mg/dl

• Pregnancy

• Seropositivity for human immunodeficiency virus

• Patients who cannot give informed consent

• Secondary malignancies other than basal cell carcinoma of the skin or carcinoma in situ within the last five years

• History of seizures or requirement for medicines, such as haldol, for controlling mental disorders

• Concurrent need for corticosteroid therapy

• Active connective tissue disease

• Pleural effusion, pericardial effusion or ascites

• Patients allergic to gentamicin

• Patients with positive PCR for hepatitis C or hepatitis B

• Patients with hypersensitivity to E. coli - derived preparations

• Patients with systemic infection at time of IL2 therapy

• Patients who previously have had more than 50% of their pelvic area irradiated

• Patients with pulmonary function tests that show diffusion capacity (corrected) < 60%, and/or forced expiratory volume in 1 second (FEV1) < 65% of predicted

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Leona Holmberg, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00006244
• Other Study ID Numbers: 1461.00; NCI-2011-01313
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 12, 2017
• Last Verified: Jun 1, 2017

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Interferons; Interferon-alpha; Aldesleukin; Interferon alpha-2; Melphalan; Interleukin-2

Study Results

Participant Flow

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Overall Participants	36
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 88.9%
>=65 years	4 11.1%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	53.56
Sex: Female, Male (Count of Participants)
Female	14 38.9%
Male	22 61.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.6%
Not Hispanic or Latino	34 94.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 5.6%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	34 94.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival in Multiple Myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2 and interferon maintenance.
Time Frame	12.9 Median Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	36
Count of Participants [Participants]	9 25%

2. Primary Outcome

Title	Initial Response to Therapy
Description	Evaluate initial response to therapy (complete remission, partial remission, stable response, or progression of disease)
Time Frame	Evaluated at Day +84-90 Post-Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	36
Patients in Complete Remission	15 41.7%
Patients in Partial Remission	8 22.2%
Patients with Stable resposne	10 27.8%
Patients with Disease Progression	3 8.3%

3. Primary Outcome

Title	Time to Disease Progression
Time Frame	12.9 years (median)

Outcome Measure Data

Analysis Population Description

Out of 36 patients, 30 have relapsed and they are used to determine this outcome measure.

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	30
Median (Full Range) [years]	1.61

4. Primary Outcome

Title	Proportion of Patients Alive and in Remission
Time Frame	12.9 Median Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	36
Count of Participants [Participants]	4 11.1%

5. Secondary Outcome

Title	Number of Patients <56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity
Description	Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by younger (< 56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.
Time Frame	First 100 days post-transplant

Outcome Measure Data

Analysis Population Description

Of the 36 patients, 20 patients were <56 years old and these 20 patients are used to determine this outcome measure.

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	20
Count of Participants [Participants]	1 2.8%

6. Secondary Outcome

Title	Number of Patients ≥56 Years Old Experiencing Grade 3-4 Regimen Related Toxicity
Description	Grade 3-4 toxicities by the Bearman common toxicity criteria, encountered by older (≥56 years old) advanced multiple myeloma patients treated with melphalan, IL2-incubated peripheral blood stem cells, and sequential IL2.
Time Frame	First 100 days post-transplant

Outcome Measure Data

Analysis Population Description

Of the 36 patients, 16 patients were ≥56 years old and these 16 are used to determine this outcome measure.

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
Measure Participants	16
Count of Participants [Participants]	0 0%

Adverse Events

Arm/Group Title	Immunotherapy Treatment
Arm/Group Description	Patients receive melphalan IV over 2-3 hours on day -2 and an infusion of IL-2-treated autologous or syngeneic peripheral blood stem cells on day 0. Beginning on day 0, patients also receive IL-2 IV continuously over 5 days followed by 2 days off. Treatment with IL-2 repeats weekly for 4 weeks. Beginning 1 month later, patients undergo maintenance therapy comprising interferon alfa SC 3 times a week in the absence of disease progression or unacceptable toxicity. melphalan: Given IV recombinant interferon alfa: Given SC aldesleukin: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion in vitro-treated peripheral blood stem cell transplantation: Undergo IL2-treated autologous or syngeneic peripheral blood stem infusion
All Cause Mortality
	Immunotherapy Treatment
	Affected / at Risk (%)	# Events
Total	27/36 (75%)
Serious Adverse Events
	Immunotherapy Treatment
	Affected / at Risk (%)	# Events
Total	10/36 (27.8%)
Blood and lymphatic system disorders
Delayed ANC Engraftment	1/36 (2.8%)
Neutropenic fever	3/36 (8.3%)
Cardiac disorders
cardiac event	2/36 (5.6%)
hypotension	1/36 (2.8%)
Gastrointestinal disorders
Nausea	2/36 (5.6%)
mucositis	1/36 (2.8%)
colitis	1/36 (2.8%)
General disorders
Fever and GI	1/36 (2.8%)
Immune system disorders
sarcoidosis/failure to thrive	1/36 (2.8%)
Infections and infestations
fever	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Immunotherapy Treatment
	Affected / at Risk (%)	# Events
Total	0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.