Active, not recruiting
Phase 1/2
A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple Myeloma
Condition(s) studied
Multiple Myeloma
Investigational drug(s) / intervention(s)
CC-220DexamethasoneDaratumumabBortezomibCarfilzomibDaratumumab - 16mg/kgBortezomib (BTZ)Daratumumab- 1800mg
CC-220: CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle.
Dexamethasone: Oral DEX 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. For subjects \>75 years old, oral DEX will be administered at 20 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Daratumumab: Specified dose on specified days
Bortezomib: Specified dose on specified days
Carfilzomib: Intravenous (IV) CFZ administered at a starting dose of 20 mg/m2 on C1D1 and C1D2; and at a dose level specified by cohort dose level thereafter Days 1, 2, 8, 9, 15, 16 of each 28-day cycle.
Daratumumab - 16mg/kg: Daratumumab (DARA) 16mg/kg by intravenous infusion on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.
Bortezomib (BTZ): Bortezomib 1.3 mg/m\^2 on Days 1, 4, 8 and 11 at cycle 1-8, and Days 1, 8 at cycle ≥9 of each 21-day cycle.
Daratumumab- 1800mg: Daratumumab (DARA) 1800 mg by subcutaneous injection on Days 1, 8, 15, and 22 at cycle 1-2, Days 1, 15 at cycle 3-6, and Day 1 at cycle ≥7 of each 28-day cycle.
Study summary
This is a multicenter, multi-country, open-label, Phase 1b/2a dose-escalation study consisting of two parts: dose escalation (Part 1) for CC-220 monotherapy, CC-220 in combination with DEX, CC-220 in combination with DEX and DARA, CC-220 in combination with DEX and BTZ and CC-220 in combination with DEX and CFZ; and the expansion of the RP2D (Part 2) for CC-220 in combination with DEX for Relapsed Refractory Multiple Myeloma and CC-220 in combination with DEX and BTZ for Newly Diagnosed Multiple Myeloma.
Eligibility
Inclusion Criteria:
1\. All subjects in RRMM cohorts must have a documented diagnosis of Multiple Myeloma and have measurable disease defined as:
1. M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP ≥0.5 g/dL or uPEP ≥200 mg/24 hours and/or
2. Light chain Multiple Myeloma without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio 2. All subjects in RRMM cohorts must have documented disease progression on or within 60 days from the last dose of their last myeloma therapy. Subjects who had CAR T therapy as their last myeloma therapy must have documented disease progression.
3\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2 3. Subject must have documented diagnosis with previously untreated symptomatic MM as defined by the criteria below (Rajkumar, 2016): MM diagnostic criteria;
\- Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma
\- Any one or more of the following myeloma defining events:
* One or more of the following myeloma-related organ dysfunction (at least one of the following);
• \[C\] Calcium elevation (serum calcium \> 0.25 mmol/L \[\> 1 mg/dL\] higher than the upper limit of laboratory normal or \> 2.75 mmol/L \[\> 11 mg/dL\])
• \[R\] Renal insufficiency (serum creatinine \> 2 mg/dl \[\> 177 μmol/L\] or creatinine clearance \< 40 ml/min)
* \[A\] Anemia (hemoglobin \< 10 g/dl or \> 2 g/dL below the lower limit of laboratory normal)
* \[B\] Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT
* One or more of the following biomarkers of malignancy:
* Clonal bone marrow plasma cell percentage\* ≥ 60%
* Abnormal serum free light-chain (FLC) ratio ≥ 100 (involved kappa) or \<0.01 (involved lambda) and involved FLC level must be ≥ 100 mg/L
* \>1 focal lesion detected by magnetic resonance imaging (MRI) (at least 5 mm in size)
AND have measurable disease, as assessed by central laboratory, defined by any of the following:
\- Immunoglobulin (Ig)G myeloma: serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
\- IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
\- Light chain multiple myeloma without measurable disease in serum or urine: serum FLC ≥ 100 mg/L and abnormal kappa lambda (κ/λ) ratio 4. Subjects in Cohort J1 are not considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation due to:
\- Age ≥65 years, OR
\- In subjects \<65 years: presence of important comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with autologous stem cell transplantation.
5\. Subjects in Cohort J2 are considered by the investigator as eligible for high-dose chemotherapy and autologous stem cell transplantation according to the institution's criteria based on age, medical history, cardiac and pulmonary status, overall health and condition, co-morbid condition(s), physical examination, and laboratory data.
Exclusion Criteria:
1\. Subject has nonsecretory multiple myeloma 2. Subjects with Plasma Cell leukemia or amyloidosis 3. Any of the following laboratory abnormalities
• Absolute neutrophil count (ANC) \<1,000/μL
• Platelet count \< 75,000/μL for Part 1. For Part 2; platelet count \< 75,000/μL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; otherwise platelet count \< 50,000/μL (transfusions are not permitted to achieve minimum platelet counts
• Corrected serum calcium \>13.5 mg/dL (\>3.4 mmol/L)
* Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT)≥2.0 x upper limit of normal (ULN)
* Serum total bilirubin and alkaline phosphatase \>1.5 x ULN
* Subjects with serious renal impairment creatinine clearance (\[CrCl\] \<45 mL/min) or requiring dialysis would be excluded 4. Subjects with peripheral neuropathy ≥Grade 2
Primary outcome measure(s)
- Number of Participants With Dose Limiting Toxicities in Part 1. — From first dose to 28 days post last dose (up to 28 days)
The dose-limiting toxicity (DLT) population includes subjects who missed no more than 4 doses of CC-220, 2 doses of DEX, 1 dose of IV DARA (Cohort E), 1 dose of BTZ (Cohort F), or 1 dose of CFZ (Cohort G1 or G2) during Cycle 1 for reasons other than DLT. This population will be used for analyzing the primary endpoint regarding the determination of the MTD.
Hematologic DLTs:
Grade 4 neutropenia (ANC \<500/μL for \>5 days) Grade 3 neutropenia (ANC \<1,000/μL) with fever ≥38.5°C Grade 4 thrombocytopenia (platelet count \<25,000/μL) or Grade 3 thrombocytopenia with bleeding or need for platelet transfusion Any other grade 4 hematologic toxicity, except anemia, not resolving to pretreatment baseline within 72 hours.
Non-hematologic DLT:
Any non-hematological toxicity ≥ Grade 3, except alopecia and nausea controlled by medical management.
- Overall Response Rate (ORR) in Cohort D and Cohort H2 — Approximately on average (Cohort D: 21.14 weeks, Cohort H2: 22.11 Weeks)
Tumor response, including progressive disease (PD) according to the IMWG Uniform Response Criteria (Kumar, 2016) for subjects who achieved partial response (PR) or better.
Trial sites (162)
| Facility | City | Region | Status |
| Local Institution - 102 |
Scottsdale |
Arizona |
|
| Mayo Clinic |
Scottsdale |
Arizona |
|
| Local Institution - 107 |
Little Rock |
Arkansas |
|
| University of Arkansas for Medical Sciences |
Little Rock |
Arkansas |
|
| Local Institution - 101 |
Atlanta |
Georgia |
|
| Winship Cancer Institute of Emory University |
Atlanta |
Georgia |
|
| Local Institution - 120 |
Chicago |
Illinois |
|
| Robert H Lurie Comprehensive Cancer Center NW Univ |
Chicago |
Illinois |
|
| Local Institution - 113 |
Fairway |
Kansas |
|
| University of Kansas Cancer Center |
Fairway |
Kansas |
|
| Local Institution - 106 |
Baltimore |
Maryland |
|
| University of Maryland School of Med |
Baltimore |
Maryland |
|
| Beth Israel Deaconess Medical Center |
Boston |
Massachusetts |
|
| Local Institution - 114 |
Boston |
Massachusetts |
|
| Local Institution - 115 |
Boston |
Massachusetts |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Dana-Farber/Mass General Brigham Cancer Care, Inc |
Boston |
Massachusetts |
|
| Local Institution - 110 |
Boston |
Massachusetts |
|
| Local Institution - 104 |
Ann Arbor |
Michigan |
|
| University of Michigan Comprehensive Cancer Center |
Ann Arbor |
Michigan |
|
| Karmanos Cancer Institute |
Detroit |
Michigan |
|
| Local Institution - 103 |
Detroit |
Michigan |
|
| Local Institution - 140 |
Grand Island |
Nebraska |
|
| Local Institution - 141 |
Grand Island |
Nebraska |
|
| Local Institution - 137 |
Omaha |
Nebraska |
|
| Local Institution - 138 |
Omaha |
Nebraska |
|
| Local Institution - 131 |
Omaha |
Nebraska |
|
| Local Institution - 139 |
Papillion |
Nebraska |
|
| Local Institution - 756 |
Cherry Hill |
New Jersey |
|
| Hackensack University Medical Center |
Hackensack |
New Jersey |
|
| Local Institution - 108 |
Hackensack |
New Jersey |
|
| Local Institution - 122 |
Mineola |
New York |
|
| NYU Winthrop Hospital |
Mineola |
New York |
|
| Local Institution - 121 |
New York |
New York |
|
| New York University School of Medicine |
New York |
New York |
|
| Icahn School of Medicine at Mount Sinai Medical Center |
New York |
New York |
|
| Local Institution - 109 |
New York |
New York |
|
| Local Institution - 111 |
New York |
New York |
|
| New York Presbyterian Hospital Weil Cornell Medical College |
New York |
New York |
|
| Local Institution - 125 |
Rochester |
New York |
|
+ 122 more sites — see the full list on the official registry below.
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