A randomized phase 3 study of Teclistamab in combination with daratumumab verses an Investigators choice of Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Velcade, Dexamethasone in Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004742-11-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 560
1. =18 years of age.
2. Documented multiple myeloma as defined by the criteria below:
a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
b. Measurable disease at screening as defined by any of the following:
1) Serum M-protein level =0.5 g/dL (central laboratory); or
2) Urine M-protein level =200 mg/24 hours (central laboratory); or
3) Serum immunoglobulin free light chain =10 mg/dL (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Received 1 to 3 prior line(s) of antimyeloma therapy (Appendix 6) including a PI and lenalidomide.
a. Participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory (ie, have demonstrated progressive disease by IMWG criteria during treatment or within 60 days
of completion of lenalidomide-containing regimen). Progression on orwithin 60 days of the last dose of lenalidomide given as maintenance will meet this criterion.
4. Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen.
5. Have an ECOG performance status score of 0, 1, or 2 at screening and immediately prior to the start of administration of study treatment (Appendix 7).
6. Have clinical laboratory values meeting the following criteria during the Screening Phase. In addition, these laboratory values must be reevaluated within the 72 hours prior to the first dose and the participant must also meet all criteria. If one or more criteria are not met 72 hours prior to dosing, one repeat of laboratory testing is permitted. If >1 repeat laboratory test is necessary, the sponsor must be consulted prior to dosing
7. A woman of childbearing potential must have a negative highlysensitive serum pregnancy test at screening and again within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study
8. A woman must be:
a. Not of childbearing potential, or
b. Of childbearing potential and
1) Practicing true abstinence; or
2) Have a sole partner who is vasectomized; or
3) Practicing =2 methods of contraception (at least 1 highly effective). For participants who are of childbearing potential and treated with DPd in Arm B, see Section 6.12.3 for details regarding concomitant use of estrogen-containing products and pomalidomide.
9. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use, for the purposes of assisted reproduction during the study and for 90 days after receiving the last dose of study treatment
10. A man must wear a condom (with or without spermicidal foam/gel/film/cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for a minimum of 90 days after receiving the last dose of study treatment. If a female partner is of childbearing potential, she must also be practicing a highly effective method of contraception.
11. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last dose of study treatment.
12. Must be willing and able to adhere to the lifestyle restrictions specified in this protocol (Section 5.3)
13. Must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
1 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the teclistamab Investigator's Brochure and appropriate package inserts), Additional exclusion criteria pertaining to specific study drugs include:
a. A participant is not eligible to receive DPd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide
2) Disease that is considered refractory to pomalidomide per IMWG (progression during treatment or within 60 days of completing treatment with pomalidomide).
b. A participant is not eligible to receive DVd as control therapy if any of the following are present:
1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib (intolerance defined as prior therapy discontinued due to any AE related to bortezomib)
2) Grade 1 peripheral neuropathy with pain or Grade =2 peripheral neuropathy as defined by NCI-CTCAE Version 5.0
3) Disease that is considered refractory to bortezomib per IMWG
4) Received a strong CYP3A4 inducer (see Section 6.12.3.3) within 5 half-lives prior to randomization.
c. A participant is not eligible for this study if they are refractory to both pomalidomide and bortezomib.
2. Received any prior BCMA-directed therapy.
3. Has disease that is considered refractory to an anti-CD38 monoclonal antibody per IMWG (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody).
4. Received the following prior antimyeloma therapy, in the specified time frame prior to randomization:
a. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or =5 half-lives, whichever is less
b. Investigational vaccine within 4 weeks
c. Monoclonal antibody therapy within 21 days
d. Cytotoxic therapy within 21 days
e. PI therapy within 14 days
f. IMiD agent therapy within 14 days
g. Radiotherapy within 14 days or focal radiation within 7 days
h. Gene-modified adoptive cell therapy within 3 months.
5. Stem cell transplant:
a. An allogeneic stem cell transplant within 6 months before randomization. in case, the pts must be off all immunosuppressive medications for =42 days without signs of graft-versus-host disease before randomization.
b. An autologous stem cell transplant within 12 weeks before randomization.
6. Received a cumulative dose of corticosteroids equivalent to =140 mg of prednisone within 14 days before randomization.
7. Received a live, attenuated vaccine within 4 weeks before randomization.
8. Myelodysplastic syndrome or active malignancies other than relapsed/refractory multiple myeloma. The only allowed exceptions are:
a. Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
c. Noninvasive cervical cancer treated within the last 24 months that is considered completely cured
d. Localized prostate cancer (N0M0):
1) With a Gleason score of =6, treated within the last 24 months, or untreated and under surveillance
2) With a Gleason score of 3+4 that has been treated >6 months prior to full study screening and considered to have a very low risk of recurrence, or
3) History of localized prostate cancer and receiving androgen deprivation
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method