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

• ClinicalTrials.gov Identifier: NCT04302324
• Recruitment Status: Recruiting
• First Posted: March 10, 2020
• Last Update Posted: June 9, 2022
• Sponsor: Weill Medical College of Cornell University
• Collaborator: Janssen Scientific Affairs, LLC
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma; Refractory Multiple Myeloma; Relapse Multiple Myeloma	Drug: Daratumumab; Drug: Clarithromycin; Drug: Pomalidomide; Drug: Dexamethasone	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Daratumumab, Clarithromycin, Pomalidomide And Dexamethasone (D-ClaPd) In Multiple Myeloma Patients Previously Exposed to Daratumumab
• Actual Study Start Date: October 28, 2021
• Estimated Primary Completion Date: April 2024
• Estimated Study Completion Date: April 2025

Arms and Interventions

Arm

Intervention/treatment

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

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.

Outcome Measures

Primary Outcome Measures :

1. Best response rate within 8 cycles of induction therapy [ Time Frame: Approximately 3 years ]
   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 :

1. Median estimate of months that participants have progression free survival [ Time Frame: Approximately 5 years ]
   Median estimate calculated using the Kaplan-Meier methodology
2. Median number of months of participant's overall survival [ Time Frame: Approximately 8 years ]
   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
3. Time to Complete Hematologic Response [ Time Frame: Approximately 3 years ]
   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.
4. Time to Hematologic progression [ Time Frame: Approximately 3 years ]
   Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for hematologic progression
5. Duration of hematologic response [ Time Frame: Approximately 3 years ]
   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.
6. Time until next treatment therapy [ Time Frame: Approximately 5 years ]
   Measured in months from the date of enrollment to the start date of subsequent treatment for relapsed/refractory multiple myeloma
7. Time to complete response (CR) [ Time Frame: Approximately 3 years ]
   Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met the criteria for CR
8. Duration of Very Good Partial Response (VGPR) [ Time Frame: Approximately 3 years ]
   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
9. Rate of minimal residual disease (MRD) negativity after 8 months [ Time Frame: Approximately 3 years ]
   Defined as a percentage of MRD-negative participants from date enrollment until 8 months after start of treatment.
10. Rate of minimal residual disease (MRD) negativity after 32 months [ Time Frame: Approximately 3 years ]
    Defined as a percentage of MRD-negative participants from date enrollment until 32 months after start of treatment.
11. Rate of improvement in response during maintenance therapy [ Time Frame: Approximately 3 years ]
    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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Kathleen P Research Nurse Coordinator, RN; 646-962-6500; kap9111@med.cornell.edu

Locations

United States, New York

Weill Cornell Medicine - Multiple Myeloma Center; Recruiting

New York, New York, United States, 10065

Contact: Research Nurse, RN 646-962-6500

Principal Investigator: Cara Rosenbaum, MD

Sponsors and Collaborators

Weill Medical College of Cornell University

Janssen Scientific Affairs, LLC

Investigators

• Principal Investigator: Cara Rosenbaum, MD; Weill Medical College of Cornell University

More Information

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT04302324
• Other Study ID Numbers: 19-12021155
• First Posted: March 10, 2020
• Last Update Posted: June 9, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Clarithromycin; Dexamethasone; Daratumumab; Pomalidomide; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anti-Bacterial Agents