Interferon Alfa and Interleukin-6 in Treating Patients With Recurrent Multiple Myeloma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00470093
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 27
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Interleukin-6 may stimulate the white blood cells to kill cancer cells. Giving interferon alfa together with interleukin-6 may kill more cancer cells.

PURPOSE: This clinical trial is studying the side effects and how well giving interferon alfa together with interleukin-6 works in treating patients with recurrent multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: recombinant interferon-α; Biological: recombinant interleukin-6	Early Phase 1

Detailed Description

OBJECTIVES:

• Determine the response rate in patients with recurrent multiple myeloma treated with recombinant interferon alfa and recombinant interleukin-6.

• Determine the safety and optimal dose of this regimen in these patients.

• Determine the toxicity of this regimen in these patients.

• Determine the impact of this regimen on clonogenic growth of myeloma cells in serial in vitro assays.

OUTLINE: This is a pilot study.

Patients receive recombinant interferon alfa subcutaneously (SC) once daily. Beginning 1 month later, patients also receive recombinant interleukin-6 SC once daily. Treatment continues for up to 6 months in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of Differentiation Therapy in Multiple Myeloma Using Interleukin-6 and Interferon-a
• Actual Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Interleukin-6 and Interferon-α Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day.

Biological: recombinant interferon-α; Biological: recombinant interleukin-6

Outcome Measures

Primary Outcome Measures

1. Response Rate as Assessed by Number of Participants With Partial or Complete Response by Bladé Criteria. [Up to 5 months]

   Number of participants with partial or complete response by Bladé criteria where partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.

2. Toxicity as Measured by Number of Participants Who Discontinued Treatment Due to Adverse Events [Up to 5 months]

   Number of participants who discontinued the protocol due to adverse events.

3. Optimal Dose of Interleukin-6 [Up to 5 months]

   Maximum tolerated dose found using a standard 3+3 dose escalation model.

4. Impact of Treatment on Growth of Myeloma Cells [Day 0, Day 14, Months 1, 2, 4, and 6 of combined therapy, and end of study]

   Percentage change in growth of in vitro myeloma cells from baseline to end of study.

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 recurrent multiple myeloma

• Must have received ≥ 2 prior therapies

PATIENT CHARACTERISTICS:

• Performance status 0-3

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Study Chair: Carol A Huff, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00470093
• Other Study ID Numbers: J0620; P30CA006973; P01CA015396; NA_00002178
• First Posted: May 7, 2007
• Last Update Posted: Nov 16, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: 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; Interferons

Study Results

Participant Flow

Pre-assignment Detail	One participant was a screen failure.

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Period Title: Overall Study
STARTED	2
COMPLETED	0
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54.5
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Response Rate as Assessed by Number of Participants With Partial or Complete Response by Bladé Criteria.
Description	Number of participants with partial or complete response by Bladé criteria where partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
Time Frame	Up to 5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Measure Participants	2
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Toxicity as Measured by Number of Participants Who Discontinued Treatment Due to Adverse Events
Description	Number of participants who discontinued the protocol due to adverse events.
Time Frame	Up to 5 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Measure Participants	2
Count of Participants [Participants]	2 100%

3. Primary Outcome

Title	Optimal Dose of Interleukin-6
Description	Maximum tolerated dose found using a standard 3+3 dose escalation model.
Time Frame	Up to 5 months

Outcome Measure Data

Analysis Population Description

This outcome cannot be evaluated as zero participants tolerated the study regimen. All participants were enrolled on the 2.5 mg arm and a maximum tolerated dose was not found.

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Measure Participants	0

4. Primary Outcome

Title	Impact of Treatment on Growth of Myeloma Cells
Description	Percentage change in growth of in vitro myeloma cells from baseline to end of study.
Time Frame	Day 0, Day 14, Months 1, 2, 4, and 6 of combined therapy, and end of study

Outcome Measure Data

Analysis Population Description

Zero participants tolerated protocol therapy and the research sample blood draws were therefore not completed as planned. Because of this, the data from this outcome could not be collected.

Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
Measure Participants	0

Adverse Events

Time Frame	Up to 5 months
Adverse Event Reporting Description	Adverse events were assessed every two weeks through the first two months of combination therapy, then monthly through the end of the study.
Arm/Group Title	Interleukin-6 and Interferon-α
Arm/Group Description	Subjects will be started on recombinant interferon-α at a dose of 3 million units SQ daily, escalating the dose by 1 million units every week as tolerated to a maximum dose of 3 million units/m2/day. Following a minimum of one month of interferon therapy with two weeks on a stable dose, subjects will begin recombinant interleukin-6 therapy at a dose of 2.5 ug/kg/day. recombinant interferon-α recombinant interleukin-6
All Cause Mortality
	Interleukin-6 and Interferon-α
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Interleukin-6 and Interferon-α
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Interleukin-6 and Interferon-α
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Gastrointestinal disorders
Nausea	2/2 (100%)	3
General disorders
Cold-like symptoms	2/2 (100%)	2
Anorexia	2/2 (100%)	4
Fever	2/2 (100%)	3
Chills	2/2 (100%)	4
Diaphoresis	2/2 (100%)	2
Fatigue	2/2 (100%)	2
Excessive sleepiness	1/2 (50%)	1
Flu-like symptoms	2/2 (100%)	2
Weight loss	1/2 (50%)	1
Dehydration	1/2 (50%)	1
Headache	2/2 (100%)	4
Insomnia	1/2 (50%)	1
Constipation	1/2 (50%)	1
Immune system disorders
Salt sensitivity	1/2 (50%)	1
Infections and infestations
Upper respiratory tract infection	1/2 (50%)	1
Investigations
Anemia	1/2 (50%)	1
Musculoskeletal and connective tissue disorders
Weakness	2/2 (100%)	4
Arthralgia	2/2 (100%)	5
Myalgia	2/2 (100%)	3
Pain - neck	1/2 (50%)	1
Nervous system disorders
Confusion	2/2 (100%)	3
Dizziness	2/2 (100%)	4
Memory loss	2/2 (100%)	3
Neuropathy	1/2 (50%)	1
Depression	1/2 (50%)	1
Reproductive system and breast disorders
Erectile dysfunction	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/2 (100%)	2
Cough	2/2 (100%)	3
Voice changes	1/2 (50%)	1
Skin and subcutaneous tissue disorders
Xerostomia	1/2 (50%)	1

Limitations/Caveats

[Not Specified]

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.