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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04302324
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Weill Medical College of Cornell University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Cara Rosenbaum, MD
Principal Investigator Affiliation Weill Medical College of Cornell University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma, Refractory Multiple Myeloma, Relapse Multiple Myeloma
Arms & Interventions

Arms

Experimental: daratumumab/clarithromycin/pomalidomide/dexamethasone

Induction 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

Interventions

Drug: - Daratumumab

Given as 1800mg via injection

Drug: - Clarithromycin

Given as 500mg oral capsule

Drug: - Pomalidomide

Given as 4mg oral capsule

Drug: - Dexamethasone

Given as 20mg IV and 20mg or 40mg oral capsule.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

New York, New York

Status

Recruiting

Address

Weill Cornell Medicine - Multiple Myeloma Center

New York, New York, 10065

Site Contact

Research Nurse, RN

kap9111@med.cornell.edu

646-962-6500