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

NCT04302324 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-12021155
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Myeloma; Refractory Multiple Myeloma; Relapse Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Very Good Partial Response Rate or better within 8 cycles of induction therapy

  Very Good Partial Response or better defined as the proportion of participants with a documented Very Good Partial Response (VGPR) or better as best response per International Myeloma Working Group (IMWG) criteria, measured from date of enrollment through the end of the 8th induction cycle.

  8 months

Secondary Outcomes (11)

• Progression-Free Survival

  Approximately 3 years

• Overall Survival

  Approximately 5 years

• Complete Response Rate or Better

  Approximately 1 year

• Time to Progression

  Approximately 3 years

• Time to Next Therapy

  Approximately 3 years

Study Arms (1)

daratumumab/clarithromycin/pomalidomide/dexamethasone

EXPERIMENTAL

Induction Phase: 8 cycles (cycle length of 28 days) * Daratumumab SC: 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 40mg PO on the day after daratumumab for Cycle 1 Days 15 and 22 40mg PO pre-daratumumab weekly for Cycle 2-6 20mg PO pre-daratumumab weekly for Cycle 7-8 Maintenance Phase (Cycle 9+): Up to 24 cycles (cycle length of 28 days) * Daratumumab 1800 mg SC on Day 1 * Pomalidomide 4mg PO on Day 1-21 * Dexamethasone 20mg PO pre-daratumumab weekly for Cycles 9 and beyond

Drug: Daratumumab SC; Drug: Clarithromycin; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab SC DRUG

Given as 1800mg via injection

Also known as: Faspro

daratumumab/clarithromycin/pomalidomide/dexamethasone

Clarithromycin DRUG

Given as 500mg oral capsule

daratumumab/clarithromycin/pomalidomide/dexamethasone

Pomalidomide DRUG

Given as 4mg oral capsule

daratumumab/clarithromycin/pomalidomide/dexamethasone

Dexamethasone DRUG

Given as 20mg IV and 20mg or 40mg oral tablets

daratumumab/clarithromycin/pomalidomide/dexamethasone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (Total bilirubin ≥ 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
• 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.

You may not qualify if:

• Prior exposure to non-daratumumab anti-CD38 monoclonal antibodies or pomalidomide. Prior pomalidomide exposure in 1 or more previous lines of therapy allowed if partial remission (PR) or better achieved. No disease progression may have occurred within 60 days of receiving 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

Weill Cornell Medicine - Multiple Myeloma Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Clarithromycin; pomalidomide; Dexamethasone

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)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Cara Rosenbaum, MD

  Weill Medical College of Cornell University

  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: March 6, 2020
• First Posted: March 10, 2020
• Study Start: October 28, 2021
• Primary Completion: December 28, 2025
• Study Completion (Estimated): December 28, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)