Trial Title:
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
NCT ID:
NCT01946477
Condition:
Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Daratumumab
Pomalidomide
Conditions: Keywords:
Multiple Myeloma, MM, cancer, oncology, hematology, plasma, neoplasm, plasmacytoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pomalidomide
Arm group label:
Pomalidomide + Dexamethasone + Daratumumab
Arm group label:
Pomalidomide + dexamethasone
Other name:
CC-4047
Intervention type:
Drug
Intervention name:
Dexamethasone
Arm group label:
Pomalidomide + Dexamethasone + Daratumumab
Arm group label:
Pomalidomide + dexamethasone
Other name:
dex
Intervention type:
Drug
Intervention name:
Daratumumab
Arm group label:
Pomalidomide + Dexamethasone + Daratumumab
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Arizona Cancer Center
Address:
City:
Tucson
Zip:
85724
Country:
United States
Facility:
Name:
Marin Oncology Associates
Address:
City:
Greenbrae
Zip:
94904-2007
Country:
United States
Facility:
Name:
Local Institution - 109
Address:
City:
Los Angeles
Zip:
90095-1670
Country:
United States
Facility:
Name:
Bay Area Cancer Research Group, LLC
Address:
City:
Pleasant Hill
Zip:
94523
Country:
United States
Facility:
Name:
Local Institution - 108
Address:
City:
Whittier
Zip:
90603
Country:
United States
Facility:
Name:
Local Institution - 138
Address:
City:
Denver
Zip:
80218
Country:
United States
Facility:
Name:
Local Institution - 120
Address:
City:
Stamford
Zip:
06902
Country:
United States
Facility:
Name:
Cancer Specialist of North Florida
Address:
City:
Jacksonville
Zip:
32256
Country:
United States
Facility:
Name:
Local Institution - 127
Address:
City:
Orlando
Zip:
32804
Country:
United States
Facility:
Name:
Local Institution - 133
Address:
City:
Pembroke Pines
Zip:
33028
Country:
United States
Facility:
Name:
Local Institution - 136
Address:
City:
Saint Petersburg
Zip:
33705
Country:
United States
Facility:
Name:
Local Institution - 134
Address:
City:
Fairway
Zip:
66205
Country:
United States
Facility:
Name:
Cotton O'Neil Clinical Research, Hematology and Oncology
Address:
City:
Topeka
Zip:
66606
Country:
United States
Facility:
Name:
Local Institution - 124
Address:
City:
Louisville
Zip:
40207
Country:
United States
Facility:
Name:
Carroll Regional Cancer Center
Address:
City:
Westminster
Zip:
21157
Country:
United States
Facility:
Name:
Saint John Hospital and Medical Center
Address:
City:
Gross Pointe
Zip:
48236
Country:
United States
Facility:
Name:
St. Luke's Hospital
Address:
City:
Kansas City
Zip:
64111
Country:
United States
Facility:
Name:
Local Institution - 110
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Local Institution - 118
Address:
City:
East Orange
Zip:
07018
Country:
United States
Facility:
Name:
Local Institution - 101
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Facility:
Name:
CR Wood Cancer Center
Address:
City:
Glens Falls
Zip:
12801
Country:
United States
Facility:
Name:
Local Institution - 130
Address:
City:
Durham
Zip:
27705
Country:
United States
Facility:
Name:
Local Institution - 123
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Facility:
Name:
Local Institution - 121
Address:
City:
Cleveland
Zip:
44111
Country:
United States
Facility:
Name:
Local Institution - 115
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Facility:
Name:
Local Institution - 122
Address:
City:
Mayfield Heights
Zip:
44124
Country:
United States
Facility:
Name:
Local Institution - 107
Address:
City:
Hershey
Zip:
17033-0850
Country:
United States
Facility:
Name:
Local Institution - 135
Address:
City:
Chattanooga
Zip:
37404
Country:
United States
Facility:
Name:
Local Institution - 131
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Local Institution - 128
Address:
City:
Lubbock
Zip:
79410
Country:
United States
Facility:
Name:
Texas Health Physicians Group
Address:
City:
Plano
Zip:
75093
Country:
United States
Facility:
Name:
Local Institution - 106
Address:
City:
Spokane
Zip:
99218
Country:
United States
Facility:
Name:
Local Institution - 113
Address:
City:
Calgary
Zip:
T2N 2T9
Country:
Canada
Facility:
Name:
Local Institution - 144
Address:
City:
Surrey
Zip:
V3V 1Z2
Country:
Canada
Facility:
Name:
Local Institution - 114
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Facility:
Name:
Local Institution - 139
Address:
City:
Moncton
Zip:
E1C 8X3
Country:
Canada
Facility:
Name:
Local Institution - 140
Address:
City:
St John's
Zip:
A1B3V6
Country:
Canada
Facility:
Name:
Local Institution - 112
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Facility:
Name:
Local Institution - 148
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Facility:
Name:
Local Institution - 117
Address:
City:
Montreal
Zip:
H3A 1A1
Country:
Canada
Facility:
Name:
Local Institution - 205
Address:
City:
Fukuoka
Zip:
810-8563
Country:
Japan
Facility:
Name:
Local Institution - 208
Address:
City:
Kamogawa
Zip:
296-8602
Country:
Japan
Facility:
Name:
Local Institution - 204
Address:
City:
Kyoto-city
Zip:
602-8566
Country:
Japan
Facility:
Name:
Local Institution - 202
Address:
City:
Nagoya
Zip:
467-8602
Country:
Japan
Facility:
Name:
Local Institution - 203
Address:
City:
Okayama
Zip:
701-1192
Country:
Japan
Facility:
Name:
Local Institution - 206
Address:
City:
Shibukawa-shi, Gunma-ken
Zip:
377-0280
Country:
Japan
Facility:
Name:
Local Institution - 207
Address:
City:
Toyohashi
Zip:
441-8570
Country:
Japan
Facility:
Name:
Local Institution - 119
Address:
City:
San Juan
Zip:
00927
Country:
Puerto Rico
Start date:
May 29, 2014
Completion date:
May 24, 2025
Lead sponsor:
Agency:
Celgene
Agency class:
Industry
Source:
Celgene
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01946477
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
https://www.bmsstudyconnect.com/s/US/English/USenHome
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm