Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, MM, cancer, oncology, hematology, plasma, neoplasm, plasmacytoma
Brief summary
This trial will evaluate the efficacy and safety of combination of pomalidomide (POM) and low-dose dexamethasone (LD-Dex) (Cohort A) or the combination of pomalidomide (POM) , daratumumab (DARA) and low-dose dexamethasone (LD-Dex) (Cohort B) in subjects with relapsed or refractory multiple myeloma who have received a first or second line treatment of lenalidomide-based therapy. This trial will test the hypothesis for Cohort A that the proportion of patients will have an Overall Response Rate (ORR) of \> 30 % to reveal that Pomalidomide is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort B that the proportion of patients will have an Overall Response Rate (ORR) of \> 70 % to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This trial will test the hypothesis for Cohort C that the proportion of patients will have an Overall Response Rate (ORR) of \>60% to reveal that POM+DARA+LD-Dex is efficacious in pretreated patients who are refractory to lenalidomide. This treatment will be in only Japanese patients.
Detailed description
A phase 2, multicenter, multi-cohort, open-label study of pomalidomide in combination with low-dose dexamethasone or pomalidomide in combination with low-dose dexamethasone and daratumumab in subjects with relapsed or refractory multiple myeloma following lenalidomide based therapy in the first or second line setting. This trial will assess, Overall Response Rate (ORR), Overall Survival (OS), Progression-Free Survival (PFS), Duration of Response (DoR), Time to Response (TTR), Time to Progression(TTP) and safety.
Interventions
DRUGDexamethasone
DRUGDaratumumab
DRUGPomalidomide
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must satisfy the following criteria to be enrolled in the study: 1. Adults (age ≥ 18 years at the time of signing the ICD) with documented diagnosis of MM and measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours). 2. Subjects enrolling in Cohort A (POM+LD-dex) must have received 2 prior treatment lines of anti-myeloma therapy. Subjects enrolling in Cohort B and Cohort C (POM+DARA+LD-dex) must have received 1 or 2 prior treatment lines of anti-myeloma therapy. 3. All subjects must have received prior treatment with LEN or a LEN-containing regimen for at least 2 consecutive cycles as the most recent treatment regimen. 4. All subjects must have documented disease progression during or after their last antimyeloma therapy. 5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 6. Subjects must understand and voluntarily sign an ICD prior to any study related assessments/procedures being conducted. 7. Subjects must be able to adhere to the study visit schedule and other protocol requirements. 8. All subjects must provide an adequate bone marrow sample at screening that definitively evaluates the presence or absence of myelodysplastic changes. 9. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of contraception\* simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study drug, while participating in the study (including during dose interruptions), and for at least 28 days after study treatment discontinuation and must agree to regular pregnancy testing during this timeframe. For subjects enrolled in Cohort B and Cohort C, pregnancy prevention and testing will continue until 3 months after last dose of daratumumab. 10. Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation. Female subjects enrolled in Cohort B and Cohort C must agree to abstain from breastfeeding and donating eggs during study participation and until 3 months after last dose of daratumumab. 11. Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study, even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B and Cohort C must agree to use a latex condom during any sexual contact with FCBP while participating in the study and until 3 months after last dose of daratumumab. 12. Males must also agree to refrain from donating semen or sperm during the treatment phase and for 28 days after discontinuation from this study treatment. Male subjects enrolled in Cohort B and Cohort C must also agree to refrain from donating semen or sperm during the treatment phase and until 3 months after last dose of daratumumab. 13. All subjects must agree to refrain from donating blood while on study therapy and for 28 days after discontinuation from this study treatment. 14. All subjects must agree not to share medication.
Exclusion criteria
The presence of any of the following will exclude a subject from study enrollment: <!-- --> 1. Any of the following laboratory abnormalities: • Absolute neutrophil count \< 1,000/μL • Platelet count \< 75,000/μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 30,000/μL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells. • Severe renal impairment (Creatinine Clearance \[CrCl\] \< 30 mL/min) requiring dialysis. * Corrected serum calcium \> 11.5 mg/dL (\> 2.8 mmol/L) * Hemoglobin \< 8 g/dL (\< 4.9 mmol/L; prior red blood cell transfusion or recombinant human erythropoietin use is permitted) * Serum SGOT/AST or SGPT/ALT \> 3.0 x the upper limit of normal (ULN) * Serum total bilirubin \> 2.0 mg/dL (34.2 μmol/L); or \> 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia 2. Prior history of malignancies, other than MM, unless the subject has been free of the disease for more than 5 years. Allowed exceptions include the following: •Basal or squamous cell carcinoma of the skin •Carcinoma in situ of the cervix or breast • Incidental histological finding of prostate cancer (TNM \[tumor, nodes, metastasis\] stage of T1a or T1b) 3. Previous therapy with pomalidomide or daratumumab 4. Hypersensitivity to thalidomide, LEN, or dex (this includes ≥ Grade 3 rash during prior thalidomide or LEN therapy) 5. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment and who have not discontinued immunosuppressive treatment for at least 4 weeks prior to initiation of study treatment and are currently dependent on such treatment. 6. Subjects with any one of the following: • Congestive heart failure (NY Heart Association Class III or IV) * Myocardial infarction within 12 months prior to starting study treatment * Unstable or poorly controlled angina pectoris, including Prinzmetal's variant angina pectoris 7. Subjects who received any of the following within 14 days of initiation of study treatment: • Major surgery (kyphoplasty is not considered major surgery) • Use of any anti-myeloma drug therapy 8. Use of any investigational agents including for the treatment of multiple myeloma within 28 days or 5 half-lives (whichever is longer) of treatment, unless approved by the sponsor. 9. Incidence of gastrointestinal disease that may significantly alter the oral absorption of Pomalidomide. 10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment 11. Any serious medical condition, laboratory abnormality, or psychiatric illness, that would preclude participation in the study, or interfere with interpretation of the study results 12. Pregnant or breastfeeding females 13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A, B, or C; or chronic hepatitis B or C All subjects will be tested for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (antiHBs), and hepatitis B core antibody (antiHBc). Subjects with the following serological testing are considered not eligible: * HBsAg positive * HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA Note: * Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc positive, viral DNA negative are eligible. For these subjects, DNA monitoring and prophylactic medication for HBV reactivation are recommended per local practice. * Subjects who are seropositive because of hepatitis B virus vaccination are eligible (anti-HBs positive, anti-HBc negative, and HBsAg negative). All subjects will be tested for hepatitis C antibody. Subjects are not eligible if known seropositive for hepatitis C virus. Note: • Subjects who are hepatitis C antibody positive but show no detectable viral RNA for 6 months prior to initiation of study treatment are eligible. 14. For subjects enrolling in Cohort B and Cohort C - Subject has known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From first dose until disease progression or end of treatment whichever occurs first (Up to 130 months) | ORR per Modified International Myeloma Working Group (mIMWG) Criteria is defined as the percentage of participants who achieve best overall response of Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours PR=≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From first dose until the first documented disease progression, or death whichever occurs first (Up to 130 months) | PFS is defined as the time from the first dose to the first documentation of disease progression according to modified International Myeloma Working Group (mIMWG) criteria or death from any cause, whichever occurs first. Disease Progression=Increase or reappearance of monoclonal protein in serum or urine meeting mIMWG progression thresholds; Increase in bone marrow plasma cell percentage consistent with disease progression; Development of new or worsening lytic bone lesions; Progressive or newly enlarging extramedullary plasmacytomas. Based on Kaplan-Meier Estimates. |
| Overall Survival (OS) | From first dose until death due to any cause (Up to 130 months) | OS is defined as the time from start of treatment until the time of death from any cause. If no death is recorded the subject will be censored at the time the subject was last known to be alive. Based on Kaplan-Meier Estimates |
| Duration of Response (DoR) | From first dose until the first documented disease progression, or death whichever occurs first (Up to 130 months) | DoR is defined as thr time from the initial documented response (partial response or better) to the first confirmed progressive disease or until death from any cause. Participants without documented progression will be censored at the time of their last response assessment. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours PR=≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours. Based on Kaplan-Meier Estimates |
| Time to Response (TTR) | From first dose until the first documented response (Up to 130 months) | TTR is defined as the time from the start of treatment to the first documented response (Partial Response, Very Good Partial Response or Complete Response) based on according to modified International Myeloma Working Group (mIMWG) criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours PR=≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours. Based on Kaplan-Meier Estimates |
| Time to Progression (TTP) | From first dose until the first documented disease progression whichever occurs first (Up to 130 months) | TTP is defined as the time from start of treatment until Progressive Disease (as determined by the site investigator according to modified International Myeloma Working Group (mIMWG) criteria). Participants not experiencing a documented progression will be censored at the time of their last response assessment. Disease Progression=Increase or reappearance of monoclonal protein in serum or urine meeting mIMWG progression thresholds; Increase in bone marrow plasma cell percentage consistent with disease progression; Development of new or worsening lytic bone lesions; Progressive or newly enlarging extramedullary plasmacytomas. Based on Kaplan-Meier Estimates |
| Number of Participants With Treatment Emergent Adverse Events (AEs) | From first dose until 28 days post last dose (Up to 120 months) | An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition occurring in a clinical investigation participant after signing of informed consent, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory test result), symptom, or disease temporally associated with the study intervention. |
Countries
Canada, Japan, Puerto Rico, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 138 Participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 31 / 56 | 51 / 112 | 8 / 18 |
| other Total, other adverse events | 56 / 56 | 112 / 112 | 18 / 18 |
| serious Total, serious adverse events | 30 / 56 | 69 / 112 | 11 / 18 |
Outcome results
None listed