Daratumumab-Based Therapy for the Treatment of Newly Diagnosed Multiple Myeloma With Kidney Failure

NCT04352205 | Terminated Phase 2 DMC FDA Drug

• 4 other identifiers: STUDY00000007NCI-2020-01133WINSHIP4949-20P30CA138292
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well daratumumab-based therapy works in treating patients with newly diagnosed multiple myeloma with kidney failure. Daratumumab-based therapy includes daratumumab, bortezomib, dexamethasone, and thalidomide or lenalidomide. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Bortezomib is a drug that prevents myeloma cells from getting rid of their waste products, leading to being targeted for death. Dexamethasone is a steroid that is commonly used, either alone or in combination with other drugs, to treat multiple myeloma. Lenalidomide and thalidomide may stop the growth of multiple myeloma by blocking the growth of new blood vessels necessary for tumor growth. Giving daratumumab, bortezomib, dexamethasone, and thalidomide or lenalidomide may be a good way to treat patients with newly diagnosed multiple myeloma with kidney failure.

Conditions

Plasma Cell Myeloma; Renal Failure

Outcome Measures

Primary Outcomes (1)

• Change in creatinine clearance

  Renal function comparisons of creatinine clearance between methods for the cohort will be conducted, with the primary objective of change from baseline, using the same formula, serving as the analysis dataset.

  Screening until end of Cycle 4 at day 1(12 weeks), each cycle=21 days

Secondary Outcomes (8)

• Pharmacokinetic parameters of Cmax

  Cycle 1 at day 1 (12 weeks) to Cycle 2 at Day 15 (12 Weeks), each cycle=21 days

• Pharmacokinetic parameters of AUC

  Starting at Cycle 1 at day 1(12 weeks) to Cycle 2 at Day 15 (12 weeks), each cycle=21 days

• Pharmacokinetic parameters of CI

  Cycle 1 at day (12 weeks) 1 to Cycle 2 at Day 15 (12 weeks), each cycle=21 days

• Incidence of adverse events

  Through study completion, an average of 1 year

• Overall response rate

  Through study completion, an average of 1 year

Study Arms (1)

Treatment (daratumumab-based treatment)

EXPERIMENTAL

Patients receive daratumumab IV weekly of cycles 1-3 and on day 1 only of cycle 4, bortezomib SC on days 1, 4, 8, and 11, and dexamethasone IV or PO on days 1-4 of cycle 1 and on day 1 of cycles 2-4 and PO on days 8 and 15 of all cycles. Beginning cycle 2, patients may also receive lenalidomide PO daily on days 1-14 or thalidomide PO QD on days 1-21. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Biological: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Thalidomide

Interventions

Bortezomib DRUG

Given SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Treatment (daratumumab-based treatment)

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Treatment (daratumumab-based treatment)

Dexamethasone DRUG

Given PO and IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (daratumumab-based treatment)

Lenalidomide DRUG

Given PO

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

Treatment (daratumumab-based treatment)

Thalidomide DRUG

Given PO

Also known as: (+)-Thalidomide, (-)-Thalidomide, .alpha.-Phthalimidoglutarimide, 2, 6-Dioxo-3-phthalimidopiperidine, Alpha-Phthalimidoglutarimide, Contergan, Distaval, Kevadon, N-(2,6-Dioxo-3-piperidyl)phthalimide, N-Phthaloylglutamimide, N-Phthalylglutamic Acid Imide, Neurosedyn, Pantosediv, Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (+)-, Phthalimide, N-(2, 6-dioxo-3-piperidyl)-, (-)-, Sedalis, Sedoval K-17, Softenon, Synovir, Talimol, Thalomid

Treatment (daratumumab-based treatment)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2014 criteria including: Clonal bone marrow plasma cells \>= 10%. In addition, the patient must meet one of the criteria in day (d)1 or d2:
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):
• Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal (ULN) or \> 2.75 mmol/L (\>11 mg/dL)
• Renal insufficiency: creatinine clearance (CrCl) \< 30 mL/min
• Anemia: hemoglobin value of \> 2 g/dL below the lower limit of normal, or a hemoglobin value \< 10 g/L
• Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI)
• Measurable disease as defined by any of the following:
• Serum M-protein level \>= 1.0 g/dL or urine M-protein level \>= 200 mg/24 hours.
• IgA, IgD, IgE, or IgM multiple myeloma: serum M-protein level \>= 0.5 g/dL or urine M-protein level \>= 200 mg/24 hours; or
• Light chain multiple myeloma without measurable disease in the urine: serum Ig free light chain (FLC) \>= 10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio
• Prior treatment to stabilize the patient with steroids up to 160 mg IV equivalents of dexamethasone is allowed
• Prior treatment to stabilize the patient with bortezomib up to 2 doses of 1.3 mg/m\^2 is allowed
• Subject agrees to refrain from blood donations during therapy on study and for 8 weeks after therapy is completed
• Female patients who:

You may not qualify if:

• Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis or primary or secondary plasma cell leukemia
• Participant has \>= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination within 21 days before initiation of protocol therapy
• Plasmapheresis within 28 days
• Platelet count =\< 75,000 cells/mm\^3 at time of screening evaluation. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
• Participants with an absolute neutrophil count (ANC) =\< 1000 cells/mm\^3 at time of screening evaluation. Growth factors may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation
• Participants with hemoglobin level \< 7.0 g/dL, at time of screening. Transfusion may be used to meet eligibility criteria within 7 days of obtaining screening evaluation
• Participants with hepatic impairment, defined as bilirubin \>= 1.5 x institutional upper limit of normal (ULN) or aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]), or alkaline phosphatase \>= 3 x institutional ULN, within 21 days of initiation of protocol therapy
• Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. once daily \[q.d.\] or its equivalent) for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
• Steroids160 mg IV equivalents of dexamethasone or bortezomib \> 2 doses of 1.3 mg/m\^2.
• Known significant cardiac abnormalities including:
• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Uncontrolled angina, arrhythmia or hypertension
• Myocardial infarction within the past six months
• Any other uncontrolled or severe cardiovascular condition
• Prior cerebrovascular event with residual neurologic deficit

Sponsors & Collaborators

• Emory University: lead
• Janssen Scientific Affairs, LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Renal Insufficiency

Interventions

Bortezomib; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; Thalidomide

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; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• R. Donald Harvey, PharmD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 20, 2020
• Study Start: May 7, 2020
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: July 1, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)