Study to compare Pomalidomide and Dexamethasone With or Without Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor.

• Register: EUCTR
• Last refreshed on: 11 January 2021
• Main ID: EUCTR2017-001618-27-GR
• Date of registration: 15/05/2017
• Prospective Registration: Yes
• Primary sponsor: European Myeloma Network (EMN)
• Public title: Study to compare Pomalidomide and Dexamethasone With or Without Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor.
• Scientific title: A Phase 3 Study Comparing Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Who Have Received at Least One Prior Line of Therapy With Both Lenalidomide and a Proteasome Inhibitor. - The APOLLO Study
• Date of first enrolment: 19/05/2017
• Target sample size: 302
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001618-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Czechia, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Serbia, Spain, Turkey

Contacts

• Name: Health Data Specialists Ireland
• Affiliation: Health Data Specialists Ireland LIMITED

• Name: Health Data Specialists Ireland
• Affiliation: Health Data Specialists Ireland LIMITED

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males and females at least 18 years of age;
2. Voluntary written informed consent before performance of any study-related procedure;
3. Subject must have measurable disease of MM as defined by the criteria below:
- IgG multiple myeloma: Serum M protein level =1.0 g/dL or urine M-protein level =200 mg/24 hours, or
- IgA, IgD, IgE, IgM multiple myeloma: Serum M-protein level =0.5 g/dL or urine M-protein level =200 mg/24 hours; or
- Light chain multiple myeloma, for subjects without measurable disease in the serum or urine: Serum immunoglobulin free light chain (FLC) =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio;
4. Subjects must have received prior anti-myeloma treatment. The prior treatment must have included both a PI- and lenalidomide-containing regimens. The subject must have had a response (ie, PR or better based on the investigator’s determination of response as defined by the modified IMWG criteria) to prior therapy;
5.Subjects must have documented evidence of PD based on the investigator’s determination of response as defined by the modified IMWG criteria on or after the last regimen;
6. Subjects who received only 1 line of prior treatment must have demonstrated PD on or within 60 days of completion of the lenalidomide containing regimen (ie, lenalidomide refractory);
7. Eastern Cooperative Oncology Group (ECOG) performance status score of = 2;
8. Willingness and ability to participate in study procedures;
9. For subjects experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to =Grade 1;
10. All of the following laboratory test results during Screening:
a) Absolute neutrophil count =1.0 × 109/L;
b) Hemoglobin level =7.5 g/dL (=4.65 mmol/L) (transfusions are not permitted to reach this level);
c) Platelet count =75 × 109/L in subjects in whom <50% of bone marrow nucleated cells are plasma cells and platelet count =50 x 109/L in subjects in whom =50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted to reach this level);
d) Alanine aminotransferase (ALT) level =2.5 times the upper limit of normal (ULN);
e) Aspartate aminotransferase (AST) level =2.5 x ULN;
f) Total bilirubin level =1.5 x ULN, (except for Gilbert Syndrome: direct bilirubin =1.5 × ULN);
g) Creatinine clearance =30 mL/min (Appendix 6);
h) Serum calcium corrected for albumin =14.0 mg/dL (=3.5 mmol/L), or free ionized calcium = 6.5 mg/dL (=1.6 mmol/L);
11. Criterion (letter “g”) modified per Amendment 2:
11.1 Reproductive Status:
a) Women of childbearing potential (WOCBP) must have 2 negative serum or urine pregnancy tests, one 10-14 days prior to start of study treatment and one within 24 hours prior to the start of study treatment. Females are not of reproductive potential if they have been in natural menopause for at least 24 consecutive months, or have had a hysterectomy and/or bilateral oophorectomy;
b) Women must not be breastfeeding;
c) WOCBP must agree to follow instructions for methods of contraception for 4 weeks before the start of study treatment, for the duration of study treatment, and for 3 months after cessation of daratumumab or 4 weeks after cessation of pomalidomide, whichever is longer;
d) Males who are sexually active must always use a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy. They must also agree to follow instructions for methods of
Exclusion criteria:
1. Previous therapy with any anti-CD38 monoclonal antibody;
2. Previous exposure to pomalidomide;
3. Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before Cycle 1, Day 1 (C1D1);
4. Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1;
5. History of malignancy (other than MM) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years);
6. Clinical signs of meningeal involvement of MM;
7. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. (Appendix 4);
8. Clinically significant cardiac disease, including:
a) Myocardial infarction within 6 months, before C1D1, or unstable or uncontrolled condition (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV);
b) Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Grade 3 or higher) or clinically significant electrocardiogram (ECG abnormalities;
c) Electrocardiogram showing a baseline QT interval as corrected QTc >470 msec;
9. Criterion modified per Amendment 2:
9.1 Known:
a) Active hepatitis A
b) To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
c) To be seropositive for hepatitis C (except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy).
10. Criterion Revised per Amendment 2
10.1 Known to be seropositive for human immunodeficiency virus.
11. Gastrointestinal disease that may significantly alter the absorption of pomalidomide;
12. Subject has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis;
13. Any concurrent medical or psychiatric condition or disease (eg, active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study;
14. Ongoing = Grade 2 peripheral neuropath

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed or Refractory Multiple Myeloma
MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: DARZALEX
Product Name: daratumumab
Product Code: daratumumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Imnovid
Product Name: pomalidomide
Product Code: pomalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Trade Name: Imnovid
Product Name: pomalidomide
Product Code: pomalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Imnovid
Product Name: pomalidomide
Product Code: pomalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Imnovid
Product Name: pomalidomide
Product Code: pomalidomide
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pomalidomide
CAS Number: 19171-19-8
Other descriptive name: POMALIDOMIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Product Name: Daratumumab co-formulated with recombinant human hyaluronidase (rHuPH20)
Pharmaceutical Form: Injection
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Other descriptive name: HUMAX-CD38
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
INN or Proposed INN: Recombina

Primary Outcome(s)

Main Objective: The primary objective of this study is to compare PFS between treatment arms.

Primary end point(s): The primary endpoint of this study is PFS (Progression-free survival).

Timepoint(s) of evaluation of this end point: For the entire duration of the study.

Secondary Objective: The secondary objectives of the study are the following:
To compare Overall Response Rates (ORR) between treatment arms; To compare duration of response (DoR) between treatment arms; To compare time to next therapy between treatment arms; To compare Overall Survival (OS) between treatment arms; To assess the safety and tolerability of the investigational combination treatment; To assess the depth of response by analyzing Minimum Residual Disease (MRD) negativity rate for CR or better and for suspected CR/ sCR; To compare health-related quality of life (HRQoL) and health utility between treatment arms; To evaluate the immunomodulatory effects of daratumumab on T cells; To evaluate daratumumab pharmacokinetics and the immunogenicity of rHuPH20.

Secondary Outcome(s)

Secondary end point(s): Secondary Endpoints:
- Overall response rate;
- VGPR or better rate;
- CR or better rate;
- MRD negativity rate;
- Time to response;
- Duration of response;
- Time to next therapy;
- Overall survival;
- Safety (adverse events);
- Scale and domain scores of the EORTC QLQ-C30 (global health status, physical functioning, emotional functioning, fatigue, pain) and EORTC QLQ-MY20 (disease symptoms, side effects of treatment);
- EQ-5D-5L health utility values;
- Immunomodulatory effects of daratumumab on T cells;
- Daratumumab pharmacokinetic concentrations (Dara IV and Dara SC);
- Daratumumab and rHuPH20 immunogenicity in subjects who receive Dara SC.

Timepoint(s) of evaluation of this end point: For the entire duration of the study.

Secondary ID(s)

EMN14/54767414MMY3013

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 05/05/2017
Contact: