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

NCT01794039 | Completed Phase 2 Results DMC

• 5 other identifiers: MC1187NCI-2013-0041212-006426MCCC Add 1P30CA015083
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Proportion of Confirmed Tumor Responses Defined to be a Partial Response or Better Noted as the Objective Status on Two Consecutive Evaluations

  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.

  Up to 2 years

Secondary Outcomes (3)

• 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

• Overall Survival

  Time from registration to death due to any cause, assessed up to 2 years

• Time to Progression

  Time from registration to the earliest date with documentation of disease progression, assessed up to 2 years

Study Arms (2)

Arm A (lenalidomide, dexamethasone)

EXPERIMENTAL

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; Drug: Lenalidomide

Arm B (pomalidomide, dexamethasone)

EXPERIMENTAL

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; Drug: Pomalidomide

Interventions

Dexamethasone DRUG

Given PO

Also known as: 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

Arm A (lenalidomide, dexamethasone); Arm B (pomalidomide, dexamethasone)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Arm A (lenalidomide, dexamethasone)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Pomalyst

Arm B (pomalidomide, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Shaji K. Kumar, M.D.
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

(507) 284-2017

Study Officials

• Shaji Kumar

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: February 18, 2013
• Study Start: March 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: August 21, 2018
• Results First Posted: August 21, 2018

Record last verified: 2018-08

Locations

US (1)