Pomalidomide or Lenalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT01794039
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 32.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well pomalidomide and dexamethasone work compared to lenalidomide and dexamethasone in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) or did not respond to previous treatment with lenalidomide (refractory). Pomalidomide and lenalidomide may help the immune system kill cancer cells and may also prevent the growth of new blood vessels that tumors need to grow. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone may also help pomalidomide and lenalidomide work better by making cancer cells more sensitive to the drugs. It is not yet known whether pomalidomide and dexamethasone or lenalidomide and dexamethasone are effective in treating patients with relapsed or refractory multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma	Drug: Dexamethasone; Drug: Lenalidomide; Drug: Pomalidomide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the confirmed response rate of the combination of lenalidomide and dexamethasone in patients with relapsed myeloma who have previously become refractory to lenalidomide. (Arm

1. 1. To assess the confirmed response rate of the combination of pomalidomide and dexamethasone in patients with relapsed myeloma who have previously become refractory to lenalidomide. (Arm B)

SECONDARY OBJECTIVES:

1. To assess the toxicity in each arm in patients with relapsed myeloma who have previously received lenalidomide.

2. To assess the response rates with pomalidomide and dexamethasone in patients relapsing on lenalidomide and dexamethasone. (Arm A) III. To assess time to progression and overall survival with each approach.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive lenalidomide orally (PO) daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B.

ARM B: Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase 2 Trial of Retreatment With Pomalidomide or Lenalidomide With Dexamethasone for Patients With Relapsed Myeloma
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (lenalidomide, dexamethasone) Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B.	Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid
Experimental: Arm B (pomalidomide, dexamethasone) Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Drug: Pomalidomide; Given PO; Other Names: 4-Aminothalidomide Actimid CC-4047 Pomalyst

Outcome Measures

Primary Outcome Measures

1. Proportion of Confirmed Tumor Responses Defined to be a Partial Response or Better Noted as the Objective Status on Two Consecutive Evaluations [Up to 2 years]

   The proportion of successes will be estimated in each arm independently by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. A confirmed tumor response is defined to be a partial response or better noted as the objective status on two consecutive evaluations while receiving lenalidomide and dexmethasone (Arm A) or pomalidomide and dexamethasone (Arm B). All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy.

Secondary Outcome Measures

1. Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after last day of study drug treatment]

   Recorded and reported for each patient, and frequency tables will be reviewed to determine adverse event patterns. These results are reported in the Adverse Events section of this CT.gov report.

2. Overall Survival [Time from registration to death due to any cause, assessed up to 2 years]

   The distribution of survival time will be estimated using the method of Kaplan-Meier. Due to an early closer from slow accrual the data from both arms was combined in survival analysis.

3. Time to Progression [Time from registration to the earliest date with documentation of disease progression, assessed up to 2 years]

   The distribution of time to progression will be estimated using the method of Kaplan-Meier. The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula

• Absolute neutrophil count >= 1000uL

• (Untransfused) platelet count >= 50000/uL

• Hemoglobin >= 8.0 g/dL

• Relapsed myeloma that previously became refractory to lenalidomide, after initial response of partial response or better to the drug; refractory is defined as progression on treatment with a dose of at least 10 mg daily for lenalidomide; greater than or equal to 180 days must have elapsed since previous lenalidomide therapy was stopped

• Measurable disease of multiple myeloma as defined by at least ONE of the following:

• Serum monoclonal protein >= 1.0 g/dL

• = 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)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Previously treated; NOTE: no limit to prior therapy provided there is adequate residual organ function

• Provide informed written consent

• Females of childbearing potential (FCBP)* must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by Revlimid Risk Evaluation and Mitigation Strategy [REMS]), 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; all study participants must be registered into the Revlimid REMS program, and be willing and able to comply with the requirements of Revlimid REMS program

• A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Willing to return to Mayo Clinic enrolling institution for follow-up

Exclusion Criteria:

• Residual toxicity of > grade 1 from prior therapy

• Other active malignancy < 1 year prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer

• Any of the following:

• Pregnant women

• Nursing women (lactating females must agree not to breast feed while taking lenalidomide)

• Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)

• Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease

• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment

• New York Heart Association classification III or IV

• Diagnosed active deep vein thrombosis (DVT) that has not been therapeutically anticoagulated

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

• Principal Investigator: Shaji Kumar, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01794039
• Other Study ID Numbers: MC1187; NCI-2013-00412; 12-006426; MCCC Add 1; MC1187; P30CA015083
• First Posted: Feb 18, 2013
• Last Update Posted: Aug 21, 2018
• Last Verified: Aug 1, 2018

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Dexamethasone acetate; Lenalidomide; Pomalidomide; Ichthammol; BB 1101

Study Results

Participant Flow

Arm/Group Title	Arm A (Lenalidomide, Dexamethasone)	Arm B (Pomalidomide, Dexamethasone)
Arm/Group Description	Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B.> > Dexamethasone: Given PO> > Lenalidomide: Given PO	Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Dexamethasone: Given PO> > Pomalidomide: Given PO
Period Title: Overall Study
STARTED	5	4
COMPLETED	5	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm A (Lenalidomide, Dexamethasone)	Arm B (Pomalidomide, Dexamethasone)	Total
Arm/Group Description	Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B.> > Dexamethasone: Given PO> > Lenalidomide: Given PO	Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.> > Dexamethasone: Given PO> > Pomalidomide: Given PO	Total of all reporting groups
Overall Participants	5	4	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67	68.5	67
Sex: Female, Male (Count of Participants)
Female	2 40%	1 25%	3 33.3%
Male	3 60%	3 75%	6 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 100%	4 100%	9 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Proportion of Confirmed Tumor Responses Defined to be a Partial Response or Better Noted as the Objective Status on Two Consecutive Evaluations
Description	The proportion of successes will be estimated in each arm independently by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. A confirmed tumor response is defined to be a partial response or better noted as the objective status on two consecutive evaluations while receiving lenalidomide and dexmethasone (Arm A) or pomalidomide and dexamethasone (Arm B). All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All patients that received treatment were evaluable for response

Arm/Group Title	Arm A (Lenalidomide, Dexamethasone)	Arm B (Pomalidomide, Dexamethasone)
Arm/Group Description	Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B. > > Dexamethasone: Given PO > > Lenalidomide: Given PO	Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. > > Dexamethasone: Given PO > > Pomalidomide: Given PO
Measure Participants	5	4
Number (95% Confidence Interval) [proportion of participants]	.4 8%	.25 6.3%

2. Secondary Outcome

Title	Number of Participants With Adverse Events, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	Recorded and reported for each patient, and frequency tables will be reviewed to determine adverse event patterns. These results are reported in the Adverse Events section of this CT.gov report.
Time Frame	Up to 30 days after last day of study drug treatment

Outcome Measure Data

Analysis Population Description

All treated patients are evaluable for Adverse Events

Arm/Group Title	Arm A (Lenalidomide, Dexamethasone)	Arm B (Pomalidomide, Dexamethasone)
Arm/Group Description	Patients receive lenalidomide PO daily on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients experiencing progressive disease may crossover to arm B. > > Dexamethasone: Given PO > > Lenalidomide: Given PO	Patients receive pomalidomide PO daily on days 1-21 and dexamethasone as in arm A. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. > > Dexamethasone: Given PO > > Pomalidomide: Given PO
Measure Participants	5	4
Count of Participants [Participants]	5 100%	4 100%

3. Secondary Outcome

Title	Overall Survival
Description	The distribution of survival time will be estimated using the method of Kaplan-Meier. Due to an early closer from slow accrual the data from both arms was combined in survival analysis.
Time Frame	Time from registration to death due to any cause, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

All patients that received Arm A or Arm B treatment.

Arm/Group Title	Arms A and B
Arm/Group Description	4 arm A patients were transferred to Arm B for further treatment. Arm A patients, that went off study for any reason, were allowed to transfer to Arm B.
Measure Participants	9
Median (95% Confidence Interval) [Months]	13.4

4. Secondary Outcome

Title	Time to Progression
Description	The distribution of time to progression will be estimated using the method of Kaplan-Meier. The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy.
Time Frame	Time from registration to the earliest date with documentation of disease progression, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

All patients that received Arm A or Arm B treatment.

Arm/Group Title	Arms A and B
Arm/Group Description	4 arm A patients were transferred to Arm B for further treatment. Arm A patients, that went off study for any reason, were allowed to transfer to Arm B
Measure Participants	9
Median (95% Confidence Interval) [Months]	10

Adverse Events

Arm/Group Title	Arm A (Lenalidomide, Dexamethasone)		Arm B (Pomalidomide, Dexamethasone)
Arm/Group Description	Lenalidomide: Given PO		Pomalidomide: Given PO
All Cause Mortality
	Arm A (Lenalidomide, Dexamethasone)		Arm B (Pomalidomide, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (Lenalidomide, Dexamethasone)		Arm B (Pomalidomide, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		2/4 (50%)
Blood and lymphatic system disorders
Anemia	0/5 (0%)	0	1/4 (25%)	1
Febrile neutropenia	0/5 (0%)	0	1/4 (25%)	1
Cardiac disorders
Acute coronary syndrome	1/5 (20%)	1	0/4 (0%)	0
Atrial fibrillation	0/5 (0%)	0	1/4 (25%)	1
Infections and infestations
Lung infection	2/5 (40%)	2	1/4 (25%)	1
Sepsis	0/5 (0%)	0	1/4 (25%)	2
Upper respiratory infection	0/5 (0%)	0	1/4 (25%)	1
Investigations
Lymphocyte count decreased	1/5 (20%)	1	0/4 (0%)	0
Neutrophil count decreased	1/5 (20%)	1	0/4 (0%)	0
Platelet count decreased	1/5 (20%)	1	0/4 (0%)	0
White blood cell decreased	1/5 (20%)	1	0/4 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/5 (20%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	0/5 (0%)	0	1/4 (25%)	1
Vascular disorders
Thromboembolic event	1/5 (20%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A (Lenalidomide, Dexamethasone)		Arm B (Pomalidomide, Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Anemia	2/5 (40%)	5	1/4 (25%)	2
Cardiac disorders
Aortic valve disease	0/5 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
Constipation	1/5 (20%)	5	2/4 (50%)	4
Diarrhea	4/5 (80%)	23	2/4 (50%)	5
Nausea	0/5 (0%)	0	1/4 (25%)	1
General disorders
Edema limbs	2/5 (40%)	4	2/4 (50%)	5
Fatigue	5/5 (100%)	36	3/4 (75%)	15
Infections and infestations
Infections and infestations - Oth spec	1/5 (20%)	1	0/4 (0%)	0
Investigations
Lymphocyte count decreased	4/5 (80%)	25	2/4 (50%)	2
Neutrophil count decreased	5/5 (100%)	18	2/4 (50%)	7
Platelet count decreased	4/5 (80%)	30	2/4 (50%)	7
White blood cell decreased	5/5 (100%)	24	3/4 (75%)	8
Metabolism and nutrition disorders
Hyperglycemia	0/5 (0%)	0	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/5 (0%)	0	1/4 (25%)	1
Myalgia	1/5 (20%)	2	0/4 (0%)	0
Nervous system disorders
Peripheral sensory neuropathy	5/5 (100%)	46	3/4 (75%)	15
Tremor	0/5 (0%)	0	1/4 (25%)	9
Psychiatric disorders
Agitation	1/5 (20%)	5	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/5 (20%)	2	0/4 (0%)	0
Hypohidrosis	1/5 (20%)	3	0/4 (0%)	0
Rash maculo-papular	1/5 (20%)	2	1/4 (25%)	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.