Multiple Myeloma, Refractory Multiple Myeloma, Relapse Multiple Myeloma
Conditions
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.
Interventions
DRUGDaratumumab SC
Given as 1800mg via injection
DRUGClarithromycin
Given as 500mg oral capsule
DRUGPomalidomide
Given as 4mg oral capsule
DRUGDexamethasone
Given as 20mg IV and 20mg or 40mg oral tablets
Sponsors
Weill Medical College of Cornell University
Janssen Scientific Affairs, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 (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.
Exclusion criteria
* 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 * Participation in other clinical trials within 30 days * History of thromboembolic event within the past 6 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Very Good Partial Response Rate or Better Within 8 Cycles of Induction Therapy | up to end of 8th induction cycle (up to approximately 224 days) | Very Good Partial Response or better defined as the number 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Approximately 3 years | Progression-Free Survival (PFS) is measured in months from the date of enrollment to the date of disease progression and/or death. Median estimate is calculated using the Kaplan-Meier methodology. |
| Complete Response Rate or Better | Approximately 1 year | The number of participants with a documented Complete Response (CR) or better, per International Myeloma Working Group (IMWG) criteria. |
| Time to Progression | 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 Progressive Disease |
| Time to Next Therapy | Approximately 3 years | Measured in months from the date of enrollment to the start date of subsequent treatment for relapsed/refractory multiple myeloma |
| Duration of Response | Approximately 3 years | Duration of Response (DoR) is defined as the time between the date of initial documentation of best response to the date of first documented evidence of disease progression. |
| Rate of Minimal Residual Disease (MRD) Negativity | Approximately 8 months | Defined as a number of MRD negative participants |
| Rate of Improvement in Response During Maintenance Therapy | Approximately 3 years | Percentage of patients that achieved an improved response during maintenance compared to end of induction. |
| Time to Best Response | Approximately 9.5 months | Measured in months between the date of enrollment and the first efficacy evaluation at which the participant has met criteria for best response per International Myeloma Working Group (IMWG) criteria. |
| Overall Response Rate | Approximately 1 year | The number of participants with a documented Overall Response (Partial Response or better), per International Myeloma Working Group (IMWG) criteria. |
| Very Good Partial Response (VGPR) Rate or Better | Approximately 1 year | The number of participants with a documented Very Good Partial Response (VGPR) Rate or better, per International Myeloma Working Group (IMWG) criteria. |
| Overall Survival | Approximately 5 years | Overall Survival (OS) is measured in months 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMateo Mejia Saldarriaga, MD
Weill Medical College of Cornell University
Participant flow
Pre-assignment details
1 participant withdrew consent prior to receiving the intervention and 1 participant was a screen fail
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Immunoglobulin Isotype IgA Kappa | 0 Participants |
| Immunoglobulin Isotype IgA Lambda | 1 Participants |
| Immunoglobulin Isotype IgD Kappa | 0 Participants |
| Immunoglobulin Isotype IgG Kappa | 4 Participants |
| Immunoglobulin Isotype IgG Lambda | 3 Participants |
| Immunoglobulin Isotype Kappa Free light Chain | 1 Participants |
| Immunoglobulin Isotype Lambda Free light Chain | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 6 / 9 |
Outcome results
None listed