Daratumumab, Azacitidine, and Dexamethasone for Treatment of Patients With Recurrent or Refractory Multiple Myeloma Previously Treated With Daratumumab

NCT04407442 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20251NCI-2020-02985
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well daratumumab, azacitidine, and dexamethasone work in treating patients with multiple myeloma that has come back (recurrent) or has not responded to treatment (refractory) and was previously treated with daratumumab. Daratumumab is an antibody made up of immune cells that attaches to a protein on myeloma cells, called cluster of differentiation 38 (CD38). CD38 is found in higher levels on tumor cells than on normal cells. Daratumumab prevents the growth of tumors who have high levels of CD38 by causing those cells to die. Chemotherapy drugs, such as azacitidine, 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 is a steroid that helps decrease inflammation and lowers the body's normal immune response to help reduce the effect of any infusion-related reactions. Giving azacitidine may help increase the levels of CD38 on the tumor cells to increase the function of daratumumab to attach to those tumor cells to help destroy them.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the proportion of participants with either a stringent complete response (sCR) + complete response (CR) + very good partial response + partial response (PR) as best response using International Myeloma Working Group (IMWG) Uniform Response Criteria for all subjects who have measurable disease and received at least 2 cycles of study treatment, and have at least 2 efficacy evaluation assessments.

  Up to 18 months

Secondary Outcomes (9)

• Number of Participants With Reported Treatment-related Adverse Events (AE)

  Up to 18 months

• Duration of Response (DOR)

  Up to 18 months

• Overall Survival (OS)

  Up to 18 months

• Progression-free Survival (PFS)

  Up to 18 months

• Change in CD38 Surface Expression of Plasma Cells

  Starting 6 days before treatment up until the end of cycle 1 (each cycle is 28 days); up to 34 days total

Study Arms (1)

Treatment (azacitidine, dexamethasone, daratumumab)

EXPERIMENTAL

PRE-INDUCTION (CYCLE 0): Patients receive azacitidine IV on days -7 to -3 in absence of disease progression or unacceptable toxicity. INDUCTION (CYCLES 1-2): Patients receive azacitidine IV on days 22-26, dexamethasone IV or orally (PO), and daratumumab subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity CONSOLIDATION (CYCLES 3-6): Patients receive azacitidine IV on days 22-26 of cycle 3 and on days 1-5 of cycles 5-6, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity MAINTENANCE (CYCLES 7+): Patients receive azacitidine IV on days 1-5, dexamethasone IV or PO, and daratumumab SC over 3-5 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity

Drug: Azacitidine; Biological: Daratumumab; Drug: Dexamethasone

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (azacitidine, dexamethasone, daratumumab)

Daratumumab BIOLOGICAL

Given SC

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

Treatment (azacitidine, dexamethasone, daratumumab)

Dexamethasone DRUG

Given IV or PO

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 (azacitidine, dexamethasone, daratumumab)

Eligibility Criteria

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

You may qualify if:

• Age \>=18 years
• Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, AND have evidence of disease progression based on IMWG criteria:
• Serum M-protein \>= 0.5 g/dL, or urine M-protein \>= 200 mg/24 hours. OR
• In the absence of measurable M-protein, serum immunoglobulin free light chain \>= 10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Relapsed from or refractory to 2 or more different prior therapies, including immunomodulatory drugs (IMiDs; e.g., thalidomide, lenalidomide) and proteasome inhibitors, chemotherapy-based regimens, monoclonal antibodies, or autologous stem cell transplantation (ASCT)
• Relapse is defined as progression of disease after an initial response (minimal response (MR) or better) to previous treatment, more than 60 days after cessation of treatment
• Refractory disease is defined as \< 25% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment
• Prior exposure to daratumumab, with most recent dose being at least 6 months prior to trial enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%)
• Demonstrates adequate organ function as defined below within 7 days of first dose of drug:
• Absolute neutrophil count \>= 1,500/microliter (mcL)
• Platelets \>= 75,000/mcL
• Total bilirubin within normal institutional limits, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) =\< 3 x institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 3 x institutional upper limit of normal

You may not qualify if:

• Diagnosed or treated for malignancy (either solid tumor or hematologic) other than multiple myeloma, except:
• Malignancy treated with curative intent and with no known active disease before enrollment
• Adequately treated non-melanoma skin cancer, lentigo maligna or in situ malignancies (including but not limited to, cervical, breast) with no evidence of disease
• Received daratumumab therapy less than 6 months prior to trial enrollment
• Primary refractory to prior daratumumab
• Subject is:
• Seropositive for human immunodeficiency virus (HIV)
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen (anti-HBc) and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• Seropositive for hepatitis C (except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy)
• Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal to minimize daratumumab-related pulmonary toxicities
• Note: FEV1 testing is required for subjects suspected of having chronic obstructive pulmonary disease and asthma. Subjects must be excluded if FEV1 \< 50% of predicted normal
• Known moderate or severe persistent asthma within the past 2 year or currently has uncontrolled asthma of any classification
• Note: Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study. FEV1 testing is required for subjects suspected of having asthma
• Concurrent medical condition or disease (e.g., active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
• Clinically significant cardiac disease, including:

Sponsors & Collaborators

• University of California, San Francisco: lead
• Janssen Pharmaceuticals: collaborator
• Multiple Myeloma Research Foundation: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Azacitidine; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate

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)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; 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

Limitations and Caveats

The study was closed to enrollment earlier than expected due to slow enrollment and change in sponsor research direction.

Results Point of Contact

• Title: Dr. Alfred Chung
• Organization: University of California, San Francisco

Alfred.Chung@ucsf.edu

(415) 353-2421

Study Officials

• Alfred Chung, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 29, 2020
• Study Start: November 30, 2020
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: April 30, 2024
• Results First Posted: April 30, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)