Lenalidomide, Dexamethasone, and Clarithromycin in Treating Patients Who Have Undergone Stem Cell Transplant for Multiple Myeloma

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00445692
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 123.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This phase II trial studies lenalidomide, dexamethasone, and clarithromycin in treating patients who have undergone stem cell transplant for multiple myeloma. Biological therapies, such as lenalidomide and clarithromycin, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone and clarithromycin may be an effective treatment for multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Refractory Plasma Cell Myeloma	Drug: Clarithromycin; Drug: Dexamethasone; Drug: Lenalidomide	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate the toxicity of the use of lenalidomide/biaxin (clarithromycin)/dexamethasone as maintenance therapy after autologous/syngeneic transplant.

2. Evaluate the median time to disease progression. III. Evaluate survival.

OUTLINE:

Patients receive clarithromycin orally (PO) twice daily (BID) and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily (QD) on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Maintenance Therapy With Lenalidomide, Dexamethasone and Clarithromycin (Biaxin) Following Autologous/Syngeneic Transplant for Multiple Myeloma
• Actual Study Start Date: Jan 10, 2007
• Actual Primary Completion Date: Apr 24, 2017
• Actual Study Completion Date: Apr 24, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (clarithromycin, dexamethasone, lenalidomide) Patients receive clarithromycin orally (PO) twice daily and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks.

Drug: Clarithromycin; Given Orally (PO); Other Names: Abbott-56268 Biaxin ; 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 Orally (PO); Other Names: CC-5013 CC5013 CDC 501 Revlimid

Outcome Measures

Primary Outcome Measures

1. Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3 [First year of therapy]

2. Time to Disease Progression [Up to 10.25 years]

   International Myeloma Working Group Uniform Response Criteria was used

Secondary Outcome Measures

1. Survival [From date of transplant until the date of death from any cause, assessed up to 10.25 years]

   number of patients alive or dead

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Any autologous or syngeneic patient who underwent high dose melphalan (>= 140 mg/m^2) therapy/peripheral blood stem cell (PBSC) or bone marrow (BM) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial which is also evaluating long-term disease free survival or survival

• Platelet count (transfusion independent) > 50,000 cells/mm^{3 and absolute granulocyte count > 1500 cells/mm}3 for 5 calendar days after recovery from high dose therapy

• Patients should be between 30 days to 120 days after transplant

• Willingness and ability to comply with Food and Drug Administration (FDA)-mandated REV ASSIST Program, Celgene System for Lenalidomide Education and Prescribing Safety

• Signing a written informed consent form

Exclusion Criteria:

• Karnofsky score less than 70

• A left ventricular ejection fraction less than 45% immediately pre transplant; patients with congestive heart disease with transplant, history of myocardial infarction (MI), or history of coronary artery disease

• Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease), serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 2.5 x upper limit of normal

• Calculated by Cockcroft-Gault formula or measured serum creatinine clearance < 25 ml/minute

• Pregnant and/or lactating females

• Patients who cannot give informed consent

• Patients with untreated systemic infection

• Patients with history prior to transplant of treatment with combination therapy Lenalidomide/Biaxin and steroid without response

• Patients allergic to lenalidomide, biaxin or dexamethasone

• Referring physician not registered with REV ASSIST program or unwilling to oversee the care of the patients on study and comply with the FDA-mandated REV ASSIST Program

• Patients unwilling to practice adequate forms of contraception if clinically indicated until 30 days after stopping therapy; male patients on study need to be consulted to use latex condoms (even if they have had a vasectomy) every time they have sex with a woman who is able to have children while they are being treated and for 30 days after stopping drugs

• Patients with >= grade 3 peripheral neuropathy

• Prior history of uncontrollable side effects to dexamethasone therapy

• A prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation

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)

• Study Protocol and Statistical Analysis Plan - Oct 28, 2011

More Information

Publications

None provided.

• Responsible Party: Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00445692
• Other Study ID Numbers: 2135.00; NCI-2010-02116; 2135.00p; 2135; 2135.00; P30CA015704
• First Posted: Mar 9, 2007
• Last Update Posted: Nov 13, 2019
• Last Verified: Oct 1, 2019

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

Study Results

Participant Flow

Pre-assignment Detail	32 patients were enrolled. 31 patients started therapy. 1 patient was consented but was deemed ineligible prior to therapy initiation.

Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin orally twice daily and dexamethasone orally once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide orally once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given Orally (PO) Dexamethasone: Given PO Lenalidomide: Given PO
Period Title: Overall Study
STARTED	31
COMPLETED	15
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin orally (PO) twice daily and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given Orally (PO) Dexamethasone: Given PO Lenalidomide: Given PO
Overall Participants	31
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	8 25.8%
Male	23 74.2%
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 6.5%
White	28 90.3%
More than one race	0 0%
Unknown or Not Reported	1 3.2%

Outcome Measures

1. Primary Outcome

Title	Episodes of Grade 3-4 Non Infectious, Non-dermatological or Non-neurological Toxicities, Episodes of Any Infections, Grade 3-4 Dermatological or Episodes of Grade 2-3 Peripheral Neuropathy Common Terminology Criteria for Adverse Events Version 3
Time Frame	First year of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin orally (PO) twice a day and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given PO Dexamethasone: Given PO Lenalidomide: Given PO
Measure Participants	31
Neutropenia	6
Thrombocytopenia	1
Deep venous thrombus/Pulmonary Embolism	1
Anemia	1
Pneumonia	4
Upper respiratory infections	12
Sinusitis/acute otitis media	3
Epiglottic appendagitis	1
Cellulitis	3
Clostridium difficile colitis	1
Vaginitis	3
Peripheral neuropathy	10
Dermal leukocytic vasculitis	1
Secondary cancer Acute Myeloid Leukemia	1
Re-occurrence of skin cancer	1

2. Primary Outcome

Title	Time to Disease Progression
Description	International Myeloma Working Group Uniform Response Criteria was used
Time Frame	Up to 10.25 years

Outcome Measure Data

Analysis Population Description

Measured among the 20 patients who progressed

Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin PO BID and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO QD on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given PO Dexamethasone: Given PO Lenalidomide: Given PO
Measure Participants	20
Median (Full Range) [months]	30.5

3. Secondary Outcome

Title	Survival
Description	number of patients alive or dead
Time Frame	From date of transplant until the date of death from any cause, assessed up to 10.25 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin orally (PO) twice daily and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given Orally (PO) Dexamethasone: Given PO Lenalidomide: Given PO
Measure Participants	31
Multiple meyloma deaths	10 32.3%
Acute Myeloid Leukemia death	1 3.2%
Lung cancer death	1 3.2%
Heart attack death	1 3.2%
Alive	18 58.1%

Adverse Events

Time Frame	10.25 years
Arm/Group Title	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
Arm/Group Description	Patients receive clarithromycin orally (PO) twice daily and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity. Lenalidomide is taken 4 hours or more after last dose of daily clarithromycin. NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks. Clarithromycin: Given Orally (PO) Dexamethasone: Given PO Lenalidomide: Given PO
All Cause Mortality
	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
	Affected / at Risk (%)	# Events
Total	13/31 (41.9%)
Serious Adverse Events
	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
	Affected / at Risk (%)	# Events
Total	11/31 (35.5%)
Blood and lymphatic system disorders
Secondary cancer, Acute Myeloid Leukemia	1/31 (3.2%)
Cardiac disorders
Peripheral edema	1/31 (3.2%)
Gastrointestinal disorders
Ileus	1/31 (3.2%)
Infections and infestations
Upper Respiratory Syncytial Virus infection	1/31 (3.2%)
Varicella-zoster virus pneumonia	1/31 (3.2%)
Cellulitis	1/31 (3.2%)
Pneumonia	2/31 (6.5%)
Pneumocystis Carinii Pneumonia	1/31 (3.2%)
H1N1 influenza / Streptococcus pneumonia	1/31 (3.2%)
Upper respiratory syncytial viurs infection/Leukocytoclastic vasculitis	1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Treatment (Clarithromycin, Dexamethasone, Lenalidomide)
	Affected / at Risk (%)	# Events
Total	19/31 (61.3%)
Infections and infestations
upper respiratory infection	11/31 (35.5%)
sinus/acute otitis	3/31 (9.7%)
cellulitis	3/31 (9.7%)
vaginitis	3/31 (9.7%)
Investigations
Neutropenia	9/31 (29%)
Nervous system disorders
Peripheral Neuropathy	10/31 (32.3%)

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.