Lenalidomide in Treating Patients With Progressive or Recurrent Multiple Myeloma After a Donor Stem Cell Transplant

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00619684
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 91
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well lenalidomide works in treating patients with progressive or recurrent multiple myeloma after a donor stem cell transplant. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing.

Condition or Disease	Intervention/Treatment	Phase
Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Drug: lenalidomide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate response of relapsed or progressive multiple myeloma to lenalidomide after allogeneic stem cell transplant.

2. Proportion of patients achieving a complete, partial or minor response.

SECONDARY OBJECTIVES:

1. Evaluate toxicity and tolerability of lenalidomide in this setting.

2. For patients with chronic graft-versus-host disease (GVHD), evaluate the response to lenalidomide.

3. Evaluate time to progression (TTP).

4. Evaluate overall survival (OS).

OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Lenalidomide Following Allogeneic Stem Cell Transplant for Multiple Myeloma Patients Who Relapse or Have Disease Progression
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lenalidomide) Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide; Given PO; Other Names: CC-5013 IMiD-1 Revlimid

Outcome Measures

Primary Outcome Measures

1. Response Rate, Defined as the Number of Patients Achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR) [Up to 9 years]

   CR: No Monoclonal Protein (MP) in the blood AND no serum/urine MP by Immunofixation (IF < 0) AND < 5% plasma cells in bone marrow aspirate. VGPR: More than 90% decrease of MP and urine M protein < 100 mg/d OR serum protein electrophoresis (SPEP)/urine protein electrophoresis(UPEP) negative but serum immunofixation (IFs) or IFu urine immunofixation (IFu) ) still positive. PR: Over 50% decrease of serum MP AND > 90% reduction in 24h urinary light chain excretion or M proteinuria < 200mg/d MR: Between 25 and 49% decrease of MP in the blood AND 50-89% reduction in 24h urinary light chain excretion (monoclonal proteinuria>200 mg/d)

Secondary Outcome Measures

1. Adverse Events, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [Up to 30 days after completion of study treatment]

   Grade 1-2 adverse events occurring in >10% of participants. Grade 3 or higher adverse events occurring in one or more participants.

2. Number of Patients Requiring Dose Interruption, Dose Reduction or Discontinuance of Lenalidomide [Up to 9 years]

   Dose interruption, dose reduction or discontinuation of lenalidomide due to toxicity, GVHD or disease progression

3. Number of Patients Who Experience Improvement in GVHD on Lenalidomide, Defined as the Reduction in Severity of GVHD as Defined by the National Institutes of Health (NIH) Consensus Criteria [Up to 9 years]

4. TTP [Up to 9 years]

   Time to Progression (TTP): Time from start of therapy to meeting the definition of Progressive Disease (PD). PD: 25% increase compared to the lowest value of: Serum MP (absolute increase at least ≥ 0.5 g/dl) Or: Urine MP (absolute increase at least > 200 mg/24h) Or: for patients without measurable MP, Serum Free Light Chain test: the difference between involved and uninvolved FLC levels (absolute increase at least >100 mg/L)

5. Overall Survival [At 1 and 2 years after starting treatment with lenalidomide]

   Kaplan-Meier estimate of survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form

• Able to adhere to the study visit schedule and other protocol requirements

• Multiple myeloma, having undergone an allogeneic stem cell transplant from a matched or mismatched related or unrelated donor and have relapsed or have disease progression

• Relapse is defined as reappearance of monoclonal protein in serum or urine by immunofixation, new or increased bone lesions or hypercalcemia

• Disease progression is define as a 25% increase in monoclonal protein in serum or a 50% increase in 24 hour urinary monoclonal protein from the lowest level attained at any time point after allogeneic transplant or new or increased bone lesions or hypercalcemia

• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study, excluding corticosteroids for GVHD

• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry

• Absolute neutrophil count >= 1.5 x 10^9/L

• Platelet count >= 50 x 10^9/L

• Serum creatinine =< 2.0 mg/dL

• Total bilirubin =< 1.5 mg/dL

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 x upper limit of normal (ULN) or =< 5 x ULN if hepatic metastases are present

• Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program; FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide

• FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy

• Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

• Able to take aspirin 81 or 325 mg daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use Coumadin or low molecular weight heparin)

• All study participants must be registered into the mandatory Revlimid REMS™ program, and be willing and able to comply with the requirements of Revlimid REMS™

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form

• Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide)

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Use of any other experimental drug or therapy within 28 days of baseline

• Known hypersensitivity to thalidomide

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs

• Resistance to prior use of lenalidomide

• Concurrent use of other anti-cancer agents or treatments

• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C

• Acute GVHD grades 3 or 4

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: William Bensinger, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00619684
• Other Study ID Numbers: 2161.00; NCI-2009-01592; 2161.00; P30CA015704
• First Posted: Feb 21, 2008
• Last Update Posted: May 18, 2017
• Last Verified: Sep 1, 2015

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 94.4%
>=65 years	1 5.6%
Sex: Female, Male (Count of Participants)
Female	5 27.8%
Male	13 72.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	18 100%
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	1 5.6%
White	17 94.4%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Response Rate, Defined as the Number of Patients Achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR)
Description	CR: No Monoclonal Protein (MP) in the blood AND no serum/urine MP by Immunofixation (IF < 0) AND < 5% plasma cells in bone marrow aspirate. VGPR: More than 90% decrease of MP and urine M protein < 100 mg/d OR serum protein electrophoresis (SPEP)/urine protein electrophoresis(UPEP) negative but serum immunofixation (IFs) or IFu urine immunofixation (IFu) ) still positive. PR: Over 50% decrease of serum MP AND > 90% reduction in 24h urinary light chain excretion or M proteinuria < 200mg/d MR: Between 25 and 49% decrease of MP in the blood AND 50-89% reduction in 24h urinary light chain excretion (monoclonal proteinuria>200 mg/d)
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	18
Complete Response (CR)	5 27.8%
Very Good Partial Response (VGPR)	2 11.1%
Partial Response (PR)	3 16.7%
Minimal Response (MR)	1 5.6%

2. Secondary Outcome

Title	Adverse Events, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Description	Grade 1-2 adverse events occurring in >10% of participants. Grade 3 or higher adverse events occurring in one or more participants.
Time Frame	Up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	18
Grade 1-2 constipation	28 155.6%
Grade 1-2 diarrhea	17 94.4%
Grade 1-2 fatigue	17 94.4%
Grade 1-2 myalgia	17 94.4%
Grade 1-2 nausea	11 61.1%
Grade 1-2 neuropathy	11 61.1%
Grade 1-2 thrombocytopenia	11 61.1%
Grade 3 pneumonia	17 94.4%
Grade 3 H1N1 influenza	11 61.1%
Grade 3 fever, hypoxia and neuropathy	6 33.3%
Grade 3 myalgia	6 33.3%
Grade 3 neuropathy	6 33.3%
Grade 3 neutropenia	44 244.4%

3. Secondary Outcome

Title	Number of Patients Requiring Dose Interruption, Dose Reduction or Discontinuance of Lenalidomide
Description	Dose interruption, dose reduction or discontinuation of lenalidomide due to toxicity, GVHD or disease progression
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

Patients enrolled on the trial who received lenalidomide treatment.

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	18
Count of Participants [Participants]	13 72.2%

4. Secondary Outcome

Title	Number of Patients Who Experience Improvement in GVHD on Lenalidomide, Defined as the Reduction in Severity of GVHD as Defined by the National Institutes of Health (NIH) Consensus Criteria
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

Patients who received lenalidomide on study

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	18
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	TTP
Description	Time to Progression (TTP): Time from start of therapy to meeting the definition of Progressive Disease (PD). PD: 25% increase compared to the lowest value of: Serum MP (absolute increase at least ≥ 0.5 g/dl) Or: Urine MP (absolute increase at least > 200 mg/24h) Or: for patients without measurable MP, Serum Free Light Chain test: the difference between involved and uninvolved FLC levels (absolute increase at least >100 mg/L)
Time Frame	Up to 9 years

Outcome Measure Data

Analysis Population Description

Patients who developed Progressive Disease while on lenalidomide treatment

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	10
Median (Full Range) [Months]	8.5

6. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate of survival
Time Frame	At 1 and 2 years after starting treatment with lenalidomide

Outcome Measure Data

Analysis Population Description

Patients enrolled on trial who received lenalidomide therapy.

Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
Measure Participants	18
Percent Overall Survival at 1 year	71 394.4%
Percent Overall Survival at 2 years	58 322.2%

Adverse Events

Time Frame	Adverse event followed for 60 days after discontinuation of lenalidomide. Survival follow up up to 4 years.
Arm/Group Title	Treatment (Lenalidomide)
Arm/Group Description	Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity. lenalidomide: Given PO
All Cause Mortality
	Treatment (Lenalidomide)
	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)
Serious Adverse Events
	Treatment (Lenalidomide)
	Affected / at Risk (%)	# Events
Total	7/18 (38.9%)
General disorders
Fever, hypoxia, neuralgia	1/18 (5.6%)	1
Nervous system disorders
Neuropathy	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	3/18 (16.7%)	3
Influenza - H1N1	2/18 (11.1%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Lenalidomide)
	Affected / at Risk (%)	# Events
Total	17/18 (94.4%)
Blood and lymphatic system disorders
Thrombocytopenia	2/18 (11.1%)	2
Ear and labyrinth disorders
Epistaxis	1/18 (5.6%)	1
Eye disorders
Dry eyes	1/18 (5.6%)	1
Gastrointestinal disorders
Diarrhea	3/18 (16.7%)	3
Anorexia	1/18 (5.6%)	1
Nausea	2/18 (11.1%)	2
Constipation	5/18 (27.8%)	5
Heartburn	1/18 (5.6%)	1
General disorders
Fatigue	3/18 (16.7%)	3
Fever	1/18 (5.6%)	1
Infections and infestations
Yeast infection	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Muscle spasm	1/18 (5.6%)	1
Myalgia	3/18 (16.7%)	3
Weakness	1/18 (5.6%)	1
Jaw popping	1/18 (5.6%)	1
Nervous system disorders
Peripheral neuropathy	2/18 (11.1%)	2
Psychiatric disorders
Depression	1/18 (5.6%)	1
Insomnia	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Rash	2/18 (11.1%)	2
Skin tightness	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.