Dexamethasone, Elotuzumab, and Pomalidomide in Treating Patients With Refractory Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT03713294
• Recruitment Status: Suspended
• First Posted: October 19, 2018
• Last Update Posted: October 25, 2021
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Study Description

Brief Summary:

This phase II trial studies how well dexamethasone, elotuzumab, pomalidomide work in treating patients with multiple myeloma that has not responded to previous treatment. 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. Immunotherapy with monoclonal antibodies, such as elotuzumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pomalidomide may stop the growth of multiple myeloma by blocking the growth of new blood vessels necessary for tumor growth. Giving dexamethasone, elotuzumab, pomalidomide may work better in treating patients with multiple myeloma.

Condition or disease	Intervention/treatment	Phase
Refractory Plasma Cell Myeloma	Drug: Dexamethasone; Biological: Elotuzumab; Drug: Pomalidomide	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the overall response rate (ORR) of utilizing elotuzumab, pomalidomide and dexamethasone in patients with disease refractory to daratumumab.

SECONDARY OBJECTIVES:

I. To determine percentage of patients achieving complete response (CR) with the elotuzumab combination.

II. To determine progression-free survival (PFS) for treatment with the elotuzumab combination.

III. To determine safety profile for treatment with the elotuzumab combination. IV. To determine the overall survival (OS) for patients receiving treatment with the elotuzumab combination.

OUTLINE:

Patients receive dexamethasone intravenously (IV) on days 1, 8, 15, and 22 of courses 1-2 and IV on day 1 and orally (PO) on days 8, 15, and 22 of subsequent courses and elotuzumab IV on days 1, 8, 15, and 22 of courses 1-2 and day 1 of subsequent courses. Patients also receive pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months until progressive disease, then every 6 months thereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Sequential Treatment of Multiple Myeloma With Antibody Therapy
• Actual Study Start Date: December 19, 2018
• Estimated Primary Completion Date: October 8, 2023
• Estimated Study Completion Date: October 8, 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment (dexamethasone, elotuzumab, pomalidomide); Patients receive dexamethasone IV on days 1, 8, 15, and 22 of courses 1-2 and IV on day 1 and orally (PO) on days 8, 15, and 22 of subsequent courses and elotuzumab IV on days 1, 8, 15, and 22 of courses 1-2 and day 1 of subsequent courses. Patients also receive pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Given intravenously (IV) and orally (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; Biological: Elotuzumab; Given intravenously (IV); Other Names: BMS-901608; Empliciti; HuLuc-63; HuLuc63; PDL-063; PDL063; Drug: Pomalidomide; Given orally (PO); Other Names: 4-Aminothalidomide; Actimid; CC-4047; Imnovid; Pomalyst

Outcome Measures

Primary Outcome Measures :

1. Overall response rate (ORR) defined as a partial response, very good partial response, complete response (CR) or stringent CR (sCR) [ Time Frame: Up to 5 years ]
   The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures :

1. Percentage of patients achieving complete response (CR) [ Time Frame: Up to 5 years ]
   Will be estimated by the number of patients who achieve a sCR or CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.
2. Progression-free survival (PFS) [ Time Frame: From time of registration to time of progression or death due to any cause assessed up to 5 years ]
   The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
3. Incidence of adverse events [ Time Frame: Up to 5 years ]
   The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.
4. Overall survival (OS) [ Time Frame: Time from registration to death due to any cause assessed up to 5 years ]
   Will be estimated using the method of Kaplan-Meier.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Pathologically confirmed diagnosis of multiple myeloma and noted to have progressive disease (International Myeloma Working Group [IMWG] criteria).
• At least one prior line of therapy.
• Disease refractory to daratumumab as defined by disease progression while on or =< 60 days of completing treatment with a daratumumab-containing regimen as part of any prior line of therapy.
• Measurable disease =< 14 days prior to registration.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
• Absolute neutrophil count (ANC) >= 1,000 cell/mm^3 without growth factor support (obtained =< 14 days prior to registration).
• Platelet >= 50,000 cells/mm^3 for patients who have bone marrow plasmacytosis < 50% or >= 30,000 cells/mm^3 for patients who have bone marrow plasmacytosis of >= 50% (obtained =< 14 days prior to registration).
• Total bilirubin =< 1.5 x upper limit of normal (ULN) unless due to Gilbert?s syndrome, in which case the direct bilirubin must be =< 1.5 x ULN (obtained =< 14 days prior to registration).
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (obtained =< 14 days prior to registration).
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT/INR or aPTT is within target range of therapy (obtained =< 14 days prior to registration).
• Calculated or measured creatinine clearance >= 30 ml/min (obtained =< 14 days prior to registration).

• Negative urine or serum pregnancy test done =< 14 days prior to registration, for persons of childbearing potential only.

  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to follow the requirements of the (Revlimid/Pomalyst) Risk Evaluation and Mitigation Strategies (REMS) program.

Exclusion Criteria:

• Non-secretory multiple myeloma (MM) or known immunoglobulin light chain (AL) amyloidosis.
• Clinically significant active infection requiring intravenous antibiotics (=< 14 days prior to registration).
• >= Grade 3 neuropathy and/or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).

• Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.

  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.

• Concurrent therapy considered investigational.

  • NOTE: Patients must not be planning to receive any radiation therapy (except localized radiation for palliative care that must be completed prior to starting Cycle 1, Day 1).

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

  • Pregnant women.
  • Nursing women (lactating females are eligible provided that they agree not to breast feed while taking lenalidomide).
  • Men or women of childbearing potential who are unwilling to employ adequate contraception.

• Other active malignancy =< 3 years prior to registration.

  • EXCEPTIONS:

    • Adequately treated basal cell or squamous cell skin cancer.
    • Any in situ cancer.
    • Adequately treated Stage I or II cancer from which the patient is currently in complete remission, or
  • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
• Major surgery =< 4 weeks prior to registration.
• History of stroke/intracranial hemorrhage =< 6 months prior to registration.
• Clinically significant cardiac illness including New York Heart Association (NYHA) Class III or Class IV heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or >= Grade 3 cardiac arrhythmias noted =< 14 days prior to registration.
• Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification.
• Exhibiting clinical signs of meningeal involvement of multiple myeloma.
• Known severe chronic obstructive pulmonary disease or asthma defined as forced expiratory volume (FEV1) in 1 second < 60% of expected.
• Prior exposure to elotuzumab.
• Prior history of disease refractory to pomalidomide.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

• Uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection.
  • Symptomatic congestive heart failure.
  • Unstable angina pectoris.
  • Cardiac arrhythmia.
  • Or psychiatric illness/social situations that would limit compliance with study requirements.

Contacts and Locations

Locations

United States, Florida

Mayo Clinic in Florida

Jacksonville, Florida, United States, 32224-9980

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Sikander Ailawadhi; Mayo Clinic

More Information

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03713294
• Other Study ID Numbers: MC1884; NCI-2018-02140 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC1884 ( Other Identifier: Mayo Clinic in Florida ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: October 19, 2018
• Last Update Posted: October 25, 2021
• Last Verified: October 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mayo Clinic:

multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Dexamethasone acetate; Pomalidomide; Elotuzumab; Ichthammol; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal