Lenalidomide Intensification in Patients With Serologic/Asymptomatic Progression of Multiple Myeloma While on Lenalidomide Maintenance

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01463670
• Collaborator: Montefiore Medical Center (Other), State University of New York - Downstate Medical Center (Other), University of Rochester (Other), Weill Medical College of Cornell University (Other), Stamford Hospital (Other), Columbia University (Other), State University of New York - Upstate Medical University (Other)
• Enrollment: 11
• Locations: 11
• Arm: 1
• Actual Duration (Months): 112.7
• Patient Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether this disease will get better if treated with higher doses of Lenalidomide even if the disease returns while taking low doses of Lenalidomide. In patients with multiple myeloma treated with Lenalidomide maintenance, the disease will return. However, the physician currently does not know if the disease would respond to treatment with higher doses of Lenalidomide. This is very important for patients with multiple myeloma because the number of drugs available to treat the disease are limited. It is important to know if Lenalidomide remains still effective and if it can still be used in this situation. This study will try to find out what effects, good and/or bad higher doses of Lenalidomide has on the patient and the disease after it has returned.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: lenalidomide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Clinical Trial of Lenalidomide Intensification in Patients With Serologic/Asymptomatic Progression of Multiple Myeloma While on Lenalidomide Maintenance
• Actual Study Start Date: Oct 28, 2011
• Actual Primary Completion Date: Mar 19, 2021
• Actual Study Completion Date: Mar 19, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: lenalidomide The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.

Drug: lenalidomide; patients will begin therapy with lenalidomide 25 mg daily, 21 days out of a 28 day schedule. All patients will be evaluated monthly after every cycle. The dose will be adjusted downward in response to side effects and according to specific guidelines. Symptomatic POD occurring at any time during the study will result in removal of the patient from the study. After 2 cycles of lenalidomide, patients with at least stable disease (SD) will continue lenalidomide indefinitely until asymptomatic POD, at which time dexamethasone will be added at a dose of 40mg weekly. On the other hand, patient with asymptomatic POD after 2 cycles of lenalidomide will have dexamethasone added at a dose of 40 mg weekly. Patients with any type of POD after any cycle that includes dexamethasone will be taken off study. Patients can remain on study on lenalidomide or lenalidomide/dexamethasone indefinitely as long as they do not have POD as stated above and they tolerate the treatment.

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [6 months]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Number of Participants Evaluated for Toxicity [every 28 days before initiation of a new cycle through study completion until disease progression up to 5 years]

   All toxicities with a maximum grade and status of ≥ grade 2 will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must be 18 years of age or above at the time of enrollment.

• Patients must show evidence of asymptomatic relapse and/or progression of disease (increasing M spike in serum or urine by consensus criteria) while on lenalidomide maintenance after HDM/ASCT as part of initial line of therapy.

• Patients who have not had an HDM/ASCT as part of initial line of therapy but who are on continuous/maintenance lenalidomide after initial therapy will be permitted on study.

• Patient must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains. Measurable disease is defined as one or more of the following: serum M-protein ≥ to 0.5 g/dl, urine M-protein ≥ 200 mg/24 h, and/or serum FLC assay: involved FLC level > 10 mg/dL with abnormal serum FLC ratio.

• Patients must have adequate organ function including: Hepatic function with Bilirubin <2x the upper limit of normal and ALT and AST < 3 x the upper limit of normal; renal function with creatinine clearance ≥ 60 ml/min using the Cockcroft-Gault formula; hematologic function as defined by an absolute neutrophil count > 1000 neutrophils per microliter, platelet > 50,000 platelets per microliter and hemoglobin of ≥ 9 gm/dL without transfusion support

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

• Females of child bearing 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 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (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. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

• Patients with symptomatic relapse and/or progression of multiple myeloma. (Appendix A).

• Patients with plasma cell leukemia.

• Karnofsky performance score less than 70% or ECOG performance status greater than 2.

• Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).

• Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ or other cancer treated with curative intent > 5 years previously. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Protocol Chairs.

• Female patients who are pregnant (positive HCG) or breastfeeding. (Lactating females must agree not to breast feed while taking lenalidomide)

• Patients seropositive for the human immunodeficiency virus (HIV).

• Prior organ transplant requiring immunosuppressive therapy.

• Patients who were previously exposed to higher doses of lenalidomide and who developed severe adverse events at higher doses that preclude incremental dosing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stamford Hospital	Stamford	Connecticut	United States	06902
2	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
3	Memoral Sloan Kettering Cancer Center	Basking Ridge	New Jersey	United States
4	Montefiore Medical Center	Bronx	New York	United States	10467
5	SUNY Downstate Medical Center	Brooklyn	New York	United States
6	North Shore LIJ	New Hyde Park	New York	United States	11040
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
8	Weill Cornell Medical Center	New York	New York	United States	10065
9	University of Rochester Medical Center	Rochester	New York	United States
10	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
11	Memoral Sloan Kettering Cancer Center at Phelps	Sleepy Hollow	New York	United States	10591

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Montefiore Medical Center
• State University of New York - Downstate Medical Center
• University of Rochester
• Weill Medical College of Cornell University
• Stamford Hospital
• Columbia University
• State University of New York - Upstate Medical University

Investigators

• Principal Investigator: Hani Hassoun, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 14, 2015

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT01463670
• Other Study ID Numbers: 11-107
• First Posted: Nov 2, 2011
• Last Update Posted: May 6, 2022
• Last Verified: Mar 1, 2021

• Keywords provided by Memorial Sloan Kettering Cancer Center: LENALIDOMIDE (CC-5013); BONE MARROW; 11-107
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Lenalidomide
Arm/Group Description	The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Lenalidomide
Arm/Group Description	The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
Overall Participants	11
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	2 18.2%
Male	9 81.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%
Not Hispanic or Latino	9 81.8%
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	2 18.2%
White	6 54.5%
More than one race	0 0%
Unknown or Not Reported	3 27.3%
Region of Enrollment (Count of Participants)
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

A total of 10 patients were evaluable for the primary endpoint of response.

Arm/Group Title	Lenalidomide
Arm/Group Description	The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
Measure Participants	10
Partial Response	1 9.1%
Minor Response	1 9.1%
Stable Disease	7 63.6%
Progression of Disease	1 9.1%

2. Secondary Outcome

Title	Number of Participants Evaluated for Toxicity
Description	All toxicities with a maximum grade and status of ≥ grade 2 will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Time Frame	every 28 days before initiation of a new cycle through study completion until disease progression up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lenalidomide
Arm/Group Description	The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
Measure Participants	11
Count of Participants [Participants]	11 100%

Adverse Events

Time Frame	2 years
Arm/Group Title	Lenalidomide
Arm/Group Description	The proposed study is designed as a Phase II, multi-center trial of lenalidomide intensification in patients with asymptomatic POD while on low dose lenalidomide maintenance after HDM/ASCT or on continuous/maintenance therapy after initial treatment.
All Cause Mortality
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)
Serious Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)
Cardiac disorders
Atrial fibrillation	1/11 (9.1%)
Eye disorders
Blurred Vision	1/11 (9.1%)
General disorders
Fever	1/11 (9.1%)
Infections and infestations
Lung infection	2/11 (18.2%)
Sepsis	1/11 (9.1%)
Skin infection	1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/11 (9.1%)
Dyspnea	1/11 (9.1%)
Vascular disorders
Thromboembolic event	2/11 (18.2%)
Other (Not Including Serious) Adverse Events
	Lenalidomide
	Affected / at Risk (%)	# Events
Total	0/11 (0%)

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.