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Multiple MyelomaPhase 2NCT04150692

Escalation of Daratumumab Frequency Following Biochemical Progression in Relapsed/Refractory Multiple Myeloma

A Phase 2 study testing Dara-SC, Blood for research assessments and Bone marrow for research assessments in people with Multiple Myeloma, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

In a small case series, the investigators identified five patients who had an initial response to standard daratumumab (weekly for 2 cycles, every other week for 4 cycles, then monthly thereafter) either as mono- or combination therapy, who then had daratumumab frequency escalated when early biochemical progression… 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?
Dara-SC, Blood for research assessments and Bone marrow for research assessments
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
8 Jan 2021to 31 Mar 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Multiple myeloma diagnosis according to IMWG criteria
  • Prior achievement of PR or better on standard daratumumab (single-agent or combination therapy)
  • On daratumumab for at least 7 months, currently on once-monthly dosing
  • Evidence of biochemical progression only, confirmed via two consecutive assessments.
  • The interval between labs would generally be 1 to 4 weeks, and the second set of labs may be the screening assessment. Biochemical progression is defined as an increase of > 25% from lowest response value in any one or more of the following:
  • Serum M-component (the absolute increase must be > 0.5 g/dL)
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  • Urine M-component (the absolute increase must be > 200 mg/24 h)
  • The difference between involved and uninvolved FLC levels (the absolute increase must be > 10 mg/dL; only in patients without measurable serum and urine M-protein levels)
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate bone marrow reserve, with ANC >1500 and Platelets >75k without transfusion or growth factors within 7 days prior to assessment
  • Adequate hepatic function, with AST and ALT ≤ 3.5 times the upper limit of normal and bilirubin ≤ 2 mg/dL
  • Creatinine clearance (CrCl) ≥ 15 mL/minute within 7 days prior to enrollment, either measured or calculated using a standard formula
  • HBV DNA Tests: Subjects who are positive for Anti-HBc or Anti-HBs will undergo testing for hepatitis B DNA by PCR. 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. During and following study treatment, subjects who have history of HBV infection will be closely monitored for clinical and laboratory signs of reactivation of HBV as specified in the Time and Events Schedule. Where required by local law, the results of HBV testing may be reported to the local health authorities.
  • Able to understand and willing to sign an IRB-approved written informed consent document

Who cannot join

  • Evidence of clinical progression/relapse over the 3 months prior to confirmed eligibility, based on centralized laboratory data performed at Washington University School of Medicine or radiographic data independently reviewed at Washington University School of Medicineas defined as:
  • Development of new soft tissue plasmacytomas or bone lesions
  • Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and at least 1 cm) increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion
  • Hypercalcemia (> 11.5 mg/dL) [2.65 mmol/L]
  • Decrease in hemoglobin of > 2 g/dL [1.25 mmol/L] not attributable to another cause as determined by investigator
  • Rise in serum creatinine by 2 mg/dL or more [177 mmol/L or more] not attributable to another cause as determined by investigator
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  • Evidence of myeloma with in the CNS
  • Diagnosis of plasma cell leukemia
  • Prior allergic reaction to daratumumab or medications used in the treatment backbone
  • Interruption in daratumumab therapy for any reason in the preceding 6 months longer than 8 weeks.
  • Pregnant or lactating females - woman and men of childbearing potential are required to employ an effective contraceptive method as outlined in the ICF
  • Concurrent malignancy other than MM requiring active treatment excluding skin cancer managed with local therapy
  • Compromised cardiovascular function defined as any of the following:
  • EKG evidence of acute ischemia;
  • EKG evidence of medically significant conduction system abnormalities;
  • history of myocardial infarction within the last 6 months;
  • unstable angina pectoris or cardiac arrhythmia; (history of Class 3 or Class 4 New York Heart Association congestive heart failure.
  • Severe persistent asthma (FEV1<60% and/or daily symptoms) or severe COPD defined clinically or by historical pulmonary function tests with an FEV1 <50% predicted
  • 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 (ie, 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) 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)
  • Any other clinically significant medical disease or condition that, in the judgement of the investigator, would prevent the participant from safely participating in the trials.

About this study

Official title: ESCALADARA: Escalation of Daratumumab Frequency Following Biochemical Progression in Relapsed/Refractory Multiple Myeloma

In a small case series, the investigators identified five patients who had an initial response to standard daratumumab (weekly for 2 cycles, every other week for 4 cycles, then monthly thereafter) either as mono- or combination therapy, who then had daratumumab frequency escalated when early biochemical progression was noted, an investigational endeavor. In this series, patients received a median of 5 additional cycles of daratumumab at an escalated frequency (range: 2-8). Additionally, the median change in involved paraprotein after one cycle of weekly-escalated dara was -40% (range: -67% to +5%), with most achieving prior partial response or stable disease.

In patients who initially have at least a partial response (PR) to daratumumab, who then have biochemical progression following de-escalation, it is conceivable that CD38 saturation is not optimized at the every 4 weeks dosing interval. The investigators believe that escalating the frequency of daratumumab in patients with biochemical progression, in this investigational setting, may recapture the initial response, delay clinical progression, and/or delay treatment changes.

Being tested
Dara-SC, Blood for research assessments, Bone marrow for research assessments
Medical subject headings
Multiple Myeloma

What participants receive

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

  • Dara-SCBiological

    -Subcutaneous daratumumab and hyaluronidase-fihj

  • Blood for research assessmentsProcedure or surgery

    -Cycle 1 Day 1, Cycle 3 Day 1, and at progression or end of study (whichever is first)

  • Bone marrow for research assessmentsProcedure or surgery

    -Cycle 1 Day 1, Cycle 3 Day 1, and at progression or end of study (whichever is first)

Study groups in NCT04150692
Study groupRoleWhat they receive
Arm 1: Dara-SC Re-EscalationExperimental-Re-escalation will include weekly dosing for two 4-week cycles (8 doses, Days 1, 8, 15, and 22 of each 28-day cycle) followed by dosing every-other-week thereafter (Days 1 and 15 of each 28-day cycle). Patients will remain on study treatment until meeting clinical progression.
Receives: Biological: Dara-SC; Procedure: Blood for research assessments; Procedure: Bone marrow for research assessments
Arm 2: Dara-SCActive comparator-Continued subcutaneous daratumumab and and hyaluronidase-fihj (1,800mg/30,000U, [Dara-SC])
Receives: Biological: Dara-SC; Procedure: Blood for research assessments; Procedure: Bone marrow for research assessments

What is being measured

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

  1. Progression-free survival (PFS)

    -Defined as the length of time between Cycle 1 Day 1 and progressive disease or death. Patients who are alive and progression-free or were lost to follow-up at the time of data analyses will be censored on the last known alive date.

    Measured: Up to 3 years following initiation of treatment (estimated to 3 years and 8 months)

Secondary outcomes (5)

  1. Overall response rate (ORR)

    -Defined as the proportion of patients with a partial response (PR) or better following first treatment with daratumumab following randomization, as defined by IMWG criteria

    Measured: Up to 6 months following initiation of treatment

  2. Proportion of patients on treatment following 3 cycles

    Measured: Completion of cycle 3 by all enrolled patients (estimated to be 12 weeks)

  3. Paraprotein change between Cycle 1 and Cycle 2 of treatment

    Measured: From cycle 1 through cycle 2 (estimated to be 8 weeks)

  4. Overall survival

    -Overall survival (OS) will be defined as time from Cycle 1 Day 1 to death due to any causes. Patients who are alive or were lost to follow-up at the time of data analyses will be censored on the last known alive date.

    Measured: Up to 2 years following treatment removal (estimated to be 2 years and 8 months)

  5. Duration of response (DOR)

    -Defined as the length of time between initial response with daratumumab following randomization and progressive disease (in responders).

    Measured: Up to 3 years following initiation of treatment (estimated to be 3 years and 8 months)

Timeline

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

  1. First posted5 Nov 2019
  2. Study start8 Jan 2021
  3. Primary completion31 Mar 2026 (estimated)
  4. Study completion31 Mar 2026 (estimated)

Why it stopped: Investigator decision

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04150692
Sponsor's protocol ID
201910200
Status last verified
Jan 2022
First submitted
31 Oct 2019
Last updated
24 Jan 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dara-SC, Blood for research assessments and Bone marrow for research assessments in people with Multiple Myeloma, run by Washington University School of Medicine.

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 15 inclusion and 22 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: withdrawn, as of the sponsor's last update on 24 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Progression-free survival (PFS) (time frame: Up to 3 years following initiation of treatment (estimated to 3 years and 8 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 NCT04150692.

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 24 Jan 2022.

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