Daratumumab, Bortezomib, and Dexamethasone Followed by Daratumumab, Ixazomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

NCT03763162 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0512NCI-2018-02830
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well daratumumab, bortezomib, and dexamethasone followed by daratumumab, ixazomib, and dexamethasone in treating patients with multiple myeloma that has come back (relapsed) or does not response to treatment (refractory). Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. 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. Bortezomib and ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving daratumumab, bortezomib, and dexamethasone followed by daratumumab, ixazomib, and dexamethasone may work better and help to control cancer in patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Will be assessed by International Myeloma Working Group Criteria (IMWG).

  From the date of first dose of any study drug treatment to the date of first documentation of progressive disease, or death due to any cause, whichever occurs first, assessed up to 18 months

Study Arms (1)

Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)

EXPERIMENTAL

Patients receive daratumumab IV over 3.5-6.5 hours on days 1, 8, and 15, bortezomib SC on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes on days 1, 8, and 15 and PO on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1 of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib; Biological: Daratumumab; Drug: Dexamethasone; Drug: Ixazomib; Other: Quality-of-Life Assessment

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, dexamethasone, ixazomib)

Daratumumab BIOLOGICAL

Given IV

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

Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)

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, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)

Ixazomib DRUG

Given PO

Also known as: MLN-2238, MLN2238

Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (daratumumab, bortezomib, dexamethasone, ixazomib)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed diagnosis of multiple myeloma
• Participants must have measurable disease, as defined by at least one of the following:
• Serum monoclonal protein M-protein level \>= 0.5 g/dL
• Urinary M-protein excretion of \>= 200 mg over a 24-hour period
• Involved free light chain level \>= 10 mg/dL, along with an abnormal free light chain ratio
• Participants must have disease that has relapsed and/or refractory after their most recent therapy, with progressive disease (PD) being defined as an increase of 25% from the lowest response value in any one or more of the following:
• Serum M-component protein (the absolute increase must be \>= 0.5 g/dL) and/or
• Urine M-component protein (the absolute increase must be \>= 200 mg/24 hours) and/or
• Only in participants without a measurable serum and urine M protein level: the difference between involved and uninvolved free light chain (FLC) levels (absolute increase) must be \> 10 mg/dL
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
• Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL) that can be attributed solely to the plasma cell proliferative disorder
• Participants with one to three lines of therapy for their disease with a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for multiple myeloma (MM) (e.g. a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy)
• Participants must have achieved a partial response or better to at least one prior line of therapy
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3 without growth factors within 2 weeks of initiation of treatment

You may not qualify if:

• Participants who received prior ixazomib at any time or daratumumab or other anti-CD38 therapies, except as part of initial therapy if this was stopped to move on to SCT and the participant did not progress on anti-CD38 treatment
• Participants are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as subject having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy)
• Participants with known allergy to any of the study medications or their analogues
• Participants planning to undergo SCT prior to PD on this study (i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant)
• Participants receiving systemic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inducers (e.g. rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization
• Participants must have completed their most recent drug therapy directed at multiple myeloma in the following timeframes:
• Antitumor therapy (chemotherapy, molecular targeted therapy, retinoid therapy, or hormonal therapy,) within 14 days of study day 1.
• Antibody therapy within 28 days of study day 1
• Investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 28 days or 5 pharmacokinetic half-lives, whichever is longer, of study day 1.
• Corticosteroids at least 14 days prior to starting therapy, except for a dose equivalent to dexamethasone of =\< 4 mg/day OR an emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days)
• Autologous stem cell transplantation at least 12 weeks prior to starting study treatment
• Allogeneic stem cell transplantation at least 24 weeks prior to starting treatment, and these Participants must also NOT have moderate to severe active acute or chronic graft versus host disease (GVHD)
• Participants with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal.
• Participants with Grade 2 or higher residual toxicities from prior therapy (including Grade 2 or higher peripheral neuropathy or any grade neuropathy with pain) with the exception of alopecia.
• Participants who have undergone major surgery within 28 days of study Day 1. NOTE: Subjects with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Takeda: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib; MLN2238

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)

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

Study Officials

• Oren C Pasvolsky, MD

  M.D. Anderson Cancer Center

  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: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 4, 2018
• Study Start: January 17, 2019
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)