Daratumumab, Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin Hydrochloride, and Lenalidomide in Treating Participants With Plasma Cell Leukemia

NCT03591744 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 18162NCI-2018-01405
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I trial studies side effects of daratumumab, bortezomib, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide in treating participants with plasma cell leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide, 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. Giving daratumumab, bortezomib, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide in treating participants with plasma cell leukemia.

Conditions

Plasma Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  Observed toxicities will be tabulated using frequencies and percentages based on the CTCAE v5.0.

  Up to 30 days

Secondary Outcomes (4)

• Overall response rate described by the International Myeloma Working Group (IMWG)

  Up to 18 months

• Duration of response

  Up to 18 months

• Overall survival rate

  From date of first dose of study drug to date of death from any cause, assessed up to 18 months

• Progression-free survival rate

  From date of first dose of study drug to date of first documented disease relapse, progression or death from any cause, whichever occurs first, up to 18 months

Study Arms (1)

Treatment (daratumumab, bortezomib, chemotherapy)

EXPERIMENTAL

Participants receive daratumumab IV on days 1, 8, 15, and 22, dexamethasone IV/PO on days 1, 2, 8, 9, 15, 16, 22, and 23, pegylated liposomal doxorubicin hydrochloride IV on day 8, lenalidomide PO daily on days 1-14, and bortezomib SC on days 1, 4, 8, and 11 of courses 1 and 2. Participants then receive daratumumab IV on days 1, and 15, dexamethasone IV/PO on days 1, 2, 8, 9, 15, 16, 22, and 23, pegylated liposomal doxorubicin hydrochloride IV on day 8, lenalidomide PO daily on days 1-14, and bortezomib SC on days 1, 4, 8, and 11 of courses 3 and 4. Courses repeat every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants may receive up to 8 courses at the discretion of treating physician.

Drug: Bortezomib; Biological: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Pegylated Liposomal Doxorubicin Hydrochloride

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, bortezomib, chemotherapy)

Daratumumab BIOLOGICAL

Given IV

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

Treatment (daratumumab, bortezomib, chemotherapy)

Dexamethasone DRUG

Given IV and 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

Treatment (daratumumab, bortezomib, chemotherapy)

Lenalidomide DRUG

Given PO

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

Treatment (daratumumab, bortezomib, chemotherapy)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposome, doxorubicin hydrochloride liposome, Duomeisu, Evacet, LipoDox, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99

Treatment (daratumumab, bortezomib, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines.
• Willingness to provide bone marrow and peripheral blood samples for research purposes. If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program and be willing to comply with its requirements.
• Karnofsky performance status (KPS) \> 60.
• Plasma cell leukemia; either newly diagnosed or relapsed: defined as the presence of \> 2 x 10\^9/L peripheral blood plasma cells or plasmacytosis accounting for \> 20% of the differential white cell count.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Absolute neutrophil count (ANC) \>= 500/mm\^3
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary ot disease involvement.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Total bilirubin =\< 2.0 x ULN (unless has Gilbert's disease).
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Aspartate aminotransferase (AST) =\< 3.0 x ULN.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Alanine aminotransferase (ALT) =\< 3.0 x ULN.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Creatinine clearance of \>= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Left ventricular ejection fraction (LVEF) \> 45%
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Hemoglobin \>= 8.0 g/dL
• Note: Transfusion support is allowed.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Seronegative for human immunodeficiency virus (HIV) antigen-antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (RPR).

You may not qualify if:

• Progression or intolerance to daratumumab, bortezomib, or lenalidomide.
• Prior stem cell transplant.
• Participant is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment.
• Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable.
• Vaccination with live attenuated vaccines within 4 weeks of first study agent administration.
• Participant is currently using or has used immunosuppressive medication within 14 days prior to the first study dose of study treatment. The following are exceptions:
• Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
• Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, computed tomography \[CT\] scan premedication).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal.
• Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification.
• Clinically significant uncontrolled illness.
• Active infection requiring intravenous antibiotics or antifungals within 14 days prior to start of study treatment.
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Washington University

St Louis, Missouri, 63110, United States

Location

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Leukemia, Plasma Cell

Interventions

Bortezomib; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; liposomal doxorubicin; Doxorubicin

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System 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; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Amrita Krishnan

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: July 19, 2018
• Study Start: October 25, 2018
• Primary Completion: October 25, 2019
• Study Completion: October 25, 2019
• Last Updated: December 19, 2018

Record last verified: 2018-12

Locations

US (5)