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A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab

NCT04302324

Description:

This is a single-center single-arm phase 2 study in which patients will receive daratumumab in combination with clarithromycin/pomalidomide/dexamethasone (D-ClaPd) until progressive disease (PD) or unacceptable toxicity, whichever comes first. This study will test the hypothesis that in patients with previous daratumumab exposure, combination therapy of clarithromycin/pomalidomide/dexamethasone (ClaPd) will yield higher Very Good Partial Response (VGPR) rates in relapsed/refractory multiple myeloma patients than historical pomalidomide/dexamethasone treatment.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab
  • Official Title: A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab

Clinical Trial IDs

  • ORG STUDY ID: 19-12021155
  • NCT ID: NCT04302324

Conditions

  • Multiple Myeloma
  • Refractory Multiple Myeloma
  • Relapse Multiple Myeloma

Interventions

DrugSynonymsArms
Daratumumabdaratumumab/clarithromycin/pomalidomide/dexamethasone
Clarithromycindaratumumab/clarithromycin/pomalidomide/dexamethasone
Pomalidomidedaratumumab/clarithromycin/pomalidomide/dexamethasone
Dexamethasonedaratumumab/clarithromycin/pomalidomide/dexamethasone

Purpose

This is a single-center single-arm phase 2 study in which patients will receive daratumumab in combination with clarithromycin/pomalidomide/dexamethasone (D-ClaPd) until progressive disease (PD) or unacceptable toxicity, whichever comes first. This study will test the hypothesis that in patients with previous daratumumab exposure, combination therapy of clarithromycin/pomalidomide/dexamethasone (ClaPd) will yield higher Very Good Partial Response (VGPR) rates in relapsed/refractory multiple myeloma patients than historical pomalidomide/dexamethasone treatment.

Trial Arms

NameTypeDescriptionInterventions
daratumumab/clarithromycin/pomalidomide/dexamethasoneExperimentalInduction Phase: 8 cycles (each cycle is 28 days) Daratumumab: 1800mg SC weekly for 8 weeks for Cycle 1 and 2 1800mg SC every 2 weeks on Day 1 and 15 for Cycle 3-6 1800mg SC every 4 weeks on Day 1 for Cycle 7-8 Clarithromycin 500mg PO BID until VGPR or 8 cycles, whichever occurs first Pomalidomide 4mg PO on Days 1-21 Dexamethasone 20mg IV as pre-medication on Day 1, 8, 15, 22 20mg PO on the day after daratumumab for Cycle 1-2 40mg PO pre-daratumumab on Day 1 and 15 for Cycle 3-6 40mg PO on non-daratumumab on Day 8 and 22 for Cycle 3-6 20mg PO pre-daratumumab on Day 1 for Cycle 7-8 Maintenance Phase: up to 24 months (each cycle is 28 days) Daratumumab 1800 mg SC on Day 1 Pomalidomide 4mg PO on Day 1-21 Dexamethasone 20mg IV pre-daratumumab on Day 1
  • Daratumumab
  • Clarithromycin
  • Pomalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed Multiple Myeloma

          -  Relapsed and/or refractory myeloma defined as follows: Relapse or progressive disease
             after at least one previous line of therapy which must include prior daratumumab. At
             least 8 doses of daratumumab in a previous line must be administered either as
             monotherapy or in combination with a daratumumab-free interval of ≥3 months AND
             patient may be daratumumab refractory defined as less than a partial remission (PR)
             achieved on prior daratumumab-based therapy or have exhibited progression within 60
             days of receiving daratumumab. If previous therapy was autologous stem cell transplant
             (SCT), over 3 months must have elapsed after SCT.

          -  Measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >0.1 g/dL serum
             free light chains, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable
             plasmacytoma(s).

          -  Females of childbearing potential(FCBP) must have a negative serum or urine pregnancy
             test within 10 - 14 days prior to and again within 24 hours of prescribing
             pomalidomide and must either commit to continued abstinence from heterosexual
             intercourse or begin TWO acceptable methods of birth control, one highly effective
             method and one additional effective method AT THE SAME TIME, at least 4 weeks before
             she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

          -  Able to take aspirin daily

          -  Life expectancy must be greater than 3 months.

          -  Be able to voluntarily sign and understand written informed consent.

          -  Absolute neutrophil count (ANC) ≥750 cells/mm3 (.75 x 109/L)

          -  Platelets count ≥ 50,000/mm3 (50 x 109/L)

          -  Serum SGOT/AST ≤ 2.0 x upper limits of normal

          -  Serum SGPT/ALT <3.0 x upper limits of normal

          -  Serum creatinine ≤ 2.5 x upper limits of normal

          -  Serum total bilirubin ≤ 1.5 x upper limits of normal

          -  All participants must be registered into the mandatory POMALYST REMS™ program and be
             willing and able to comply with the requirements of the POMALYST REMS™ program.

        Exclusion Criteria:

          -  Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies or pomalidomide

          -  New York Heart Association (NYHA) Class III or IV heart failure, unstable cardiac
             arrhythmia, or unstable angina

          -  Myocardial infarction within the past 6 months

          -  Severe obstructive airway disease

          -  Planned high-dose chemotherapy and autologous stem cell transplantation within 6,
             28-day treatment cycles after starting on treatment

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects
             of prior chemotherapy

          -  Major surgery within 14 days before enrollment

          -  Radiotherapy within 14 days before enrollment (if area involved is small than within 7
             days)

          -  Systemic treatment, within 14 days before the first dose, with strong CYP3A inducers
             (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of
             Ginkgo biloba or St. John's wort

          -  Seropositive for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol

          -  Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent

          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection

          -  Patient has greater than Grade 3 peripheral neuropathy, or Grade 2 pain

          -  Participation in other clinical trials within 30 days

          -  History of thromboembolic event within the past 6 months prior to enrollment
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best response rate within 8 cycles of induction therapy
Time Frame:Approximately 3 years
Safety Issue:
Description:Best response rate defined as the proportion of participants with a documented response of partial response (PR) or better, per International Myeloma Working Group (IMWG) criteria measured from date of enrollment until end date of the 8th cycle of induction therapy.

Secondary Outcome Measures

Measure:Median estimate of months that participants have progression free survival
Time Frame:Approximately 5 years
Safety Issue:
Description:Median estimate calculated using the Kaplan-Meier methodology
Measure:Median number of months of participant's overall survival
Time Frame:Approximately 8 years
Safety Issue:
Description:Overall survival (OS) is measured from the date of enrollment to the date of the participant's death. Greenwood's formula will be used to calculate 95% confidence intervals for the Kaplan-Meier survival estimates
Measure:Time to Complete Hematologic Response
Time Frame:Approximately 3 years
Safety Issue:
Description:Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic complete response.
Measure:Time to Hematologic progression
Time Frame:Approximately 3 years
Safety Issue:
Description:Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression
Measure:Duration of hematologic response
Time Frame:Approximately 3 years
Safety Issue:
Description:Duration of hematologic response is defined as the time between the date of initial documentation of hematologic response to the date of first documented evidence of hematologic progressive disease.
Measure:Time until next treatment therapy
Time Frame:Approximately 5 years
Safety Issue:
Description:Measured in months from the date of enrollment to the start date of subsequent treatment for relapsed/refractory multiple myeloma
Measure:Time to complete response (CR)
Time Frame:Approximately 3 years
Safety Issue:
Description:Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for CR
Measure:Duration of Very Good Partial Response (VGPR)
Time Frame:Approximately 3 years
Safety Issue:
Description:Duration of hematologic VGPR is defined as the time between the date of initial documentation of hematologic VGPR to the date of first documented evidence of hematologic progressive disease
Measure:Rate of minimal residual disease (MRD) negativity after 8 months
Time Frame:Approximately 3 years
Safety Issue:
Description:Defined as a percentage of MRD-negative participants from date enrollment until 8 months after start of treatment.
Measure:Rate of minimal residual disease (MRD) negativity after 32 months
Time Frame:Approximately 3 years
Safety Issue:
Description:Defined as a percentage of MRD-negative participants from date enrollment until 32 months after start of treatment.
Measure:Rate of improvement in response during maintenance therapy
Time Frame:Approximately 3 years
Safety Issue:
Description:Defined as percentage of patients that achieved a better response rate per International Myeloma Working Group (IMWG) criteria from initial documentation of response on date of enrollment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Weill Medical College of Cornell University

Last Updated

April 21, 2020