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Multiple MyelomaPhase 2NCT01985126

An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD

A Phase 2 study testing Daratumumab 16 mg/kg (Part 1), Daratumumab 8 mg/kg (Part 1) and Methylprednisolone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 23 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab 16 mg/kg (Part 1), Daratumumab 8 mg/kg (Part 1) and Methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
23 sitesin 3 countries
Study dates
27 Sep 2013to 30 May 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented multiple myeloma according to protocol-defined criteria
  • Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria
  • Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
  • Laboratory values and electrocardiogram within protocol-defined parameters at screening

Who cannot join

  • Received daratumumab or other anti-CD38 therapies previously
  • Nonsecretory multiple myeloma
  • Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks
  • Exhibiting clinical signs of meningeal involvement of multiple myeloma
  • Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years
  • Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C
  • Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis

Trial locations and contacts

23 sites in 3 countries.

23 sites in 3 countries

United States15 sites

  • Study site

    Atlanta, Georgia

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Charlotte, North Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Detroit, Michigan

  • Study site

    Duarte, California

  • Study site

    Houston, Texas

  • Study site

    Los Angeles, California

  • Study site

    Louisville, Kentucky

  • Study site

    Madison, Wisconsin

  • Study site

    Nashville, Tennessee

  • Study site

    New Brunswick, New Jersey

  • Study site

    New York, New York

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Portland, Oregon

Other trials in United States

Canada5 sites

  • Study site

    Calgary, Alberta

  • Study site

    Edmonton, Alberta

  • Study site

    Halifax, Nova Scotia

  • Study site

    Montreal, Quebec

  • Study site

    Vancouver, British Columbia

Other trials in Canada

Spain3 sites

  • Study site

    Barcelona

  • Study site

    Salamanca

  • Study site

    Valencia

Other trials in Spain

About this study

Official title: An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or Are Double Refractory to a Proteasome Inhibitor and an IMiD

The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD.

Read the detailed description

This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.

Being tested
Daratumumab 16 mg/kg (Part 1), Daratumumab 8 mg/kg (Part 1), Methylprednisolone, Acetaminophen, Diphenhydramine
Keywords
Multiple myeloma, Daratumumab, Proteasome inhibitor, Immunomodulatory drug, IMiD
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daratumumab 16 mg/kg (Part 1)Drug

    Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion

  • Daratumumab 8 mg/kg (Part 1)Drug

    Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion

  • MethylprednisoloneDrug

    Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted

  • AcetaminophenDrug

    650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.

  • DiphenhydramineDrug

    25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.

  • Daratumumab (Part 2)Drug

    Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.

Study groups in NCT01985126
Study groupRoleWhat they receive
Part 1ExperimentalDuring Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
Receives: Drug: Daratumumab 16 mg/kg (Part 1); Drug: Daratumumab 8 mg/kg (Part 1); Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine
Part 2ExperimentalBased on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Receives: Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Daratumumab (Part 2)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Overall Response

    Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.

    Measured: Up to 14.4 Months

Secondary outcomes (6)

  1. Duration of Response

    Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be >=0.5 g/dL) and/or; urine M-component (the absolute increase must be >=200 mg/24 hours) and/or; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter [mmol/L]) that can be attributed solely to the plasma cell proliferative disorder.

    Measured: Up to 14.4 Months

  2. Overall Survival

    Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.

    Measured: Approximately up to 3 years

  3. Percentage of Participants With Clinical Benefit

    Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: >=25% but <= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.

    Measured: Up to 14.4 Months

  4. Time to Response

    Time to response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better).

    Measured: Up to 14.4 Months

  5. Progression Free Survival

    Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.

    Measured: Up to 14.4 Months

  6. Time to Disease Progression

    Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.

    Measured: Up to 14.4 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2013 (estimated)
  2. Study start27 Sep 2013
  3. Primary completion9 Jan 2015
  4. Study completion30 May 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01985126
Sponsor's protocol ID
CR102651
Other IDs
54767414MMY2002, 2013-000752-18
Status last verified
Jun 2018
First submitted
22 Jul 2013
Last updated
25 Jun 2018
Data monitoring committee
Yes
FDA-regulated device
No

Publications

  • Li X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6.

    PubMed 37022569

  • Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. doi: 10.1016/S2352-3026(20)30081-8.

    PubMed 32470437

  • Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, Abraham Y, Ceulemans H, Chiu C, Vanhoof G, Usmani SZ, Plesner T, Lonial S, Nijhof I, Lokhorst HM, Mutis T, van de Donk NWCJ, Sasser AK, Casneuf T. High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action. Cytometry A. 2019 Mar;95(3):279-289. doi: 10.1002/cyto.a.23693. Epub 2018 Dec 11.

    PubMed 30536810

  • Usmani SZ, Khan I, Chiu C, Foureau D, Druhan LJ, Rigby K, Casneuf T, Sasser AK. Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. Exp Hematol Oncol. 2018 Feb 7;7:3. doi: 10.1186/s40164-018-0096-7. eCollection 2018.

    PubMed 29445583

  • Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016 Aug 18;128(7):959-70. doi: 10.1182/blood-2016-03-703439. Epub 2016 Jun 15.

    PubMed 27307294

  • Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Blade J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.

    PubMed 26778538

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab 16 mg/kg (Part 1), Daratumumab 8 mg/kg (Part 1) and Methylprednisolone in people with Multiple Myeloma, run by Janssen Research & Development, LLC at 23 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Overall Response (time frame: Up to 14.4 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01985126, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2018.

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