A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA, versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects with Relapsed and Lenalidomide-Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma / symptomatic plasma cell disorder10018865
- Registration Number
- NL-OMON54594
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
- Have documented diagnosis of Multiple myeloma diagnosis according to the IMWG
diagnostic criteria
- Measurable disease at screening as defined by any of the following:
* Serum monoclonal paraprotein (M-protein) level >=0.5 g/dL or urine M-protein
level >=200 mg/24 hours; or
* Light chain MM without measurable M-protein in the serum or the urine: Serum
free light chain >=10 mg/dL and abnormal serum free light chain ratio.
- Have received 1 to 3 prior lines of therapy including a PI and IMiD. Subject
must have undergone at least 1 complete cycle of treatment for each line of
therapy, unless PD was the best response to the line of therapy
- PD per IMWG criteria <=6 months of last.
- Subjects with only 1 prior line of therapy must have progressed within 36
months of a stem cell transplant or if not transplanted, then within 42 months
of starting initial therapy.
- Be refractory to lenalidomide per IMWG consensus guidelines ((failure to
achieve minimal response or progression on or within 60 days of completing
lenalidomide therapy). Progression on or within 60 days of the last dose of
lenalidomide given as maintenance will meet this criterion. For subjects with
more than 1 prior line of therapy, there is no requirement to be lenalidomide
refractory to the most recent line of prior therapy. However, participants must
be refractory to lenalidomide in at least one prior line.
- Have an ECOG Performance Status score of 0 or 1
- Have clinical laboratory values as specified in the protocol.
- Women of childbearing potential must have 2 negative pregnancy tests before
start treatment
- When a woman is of childbearing potential, the subject must commit either to
abstaining
continuously from heterosexual intercourse or agree to use 2 methods of
reliable birth
control simultaneously.
- A man who is sexually active with a woman of childbearing potential or a
pregnant
woman must agree to use a barrier method of contraception (condom)
- Women and men must agree not to donate eggs or sperm, respectively, during
the study and for at least 3 months after receiving the last dose of
daratumumab or bortezomib, or 28 days after the last dose of pomalidomide,
whichever is later (Arm A) or at least 1 year after receiving a JNJ-68284528
infusion or at least 3 months after receiving the last dose of daratumumab or
bortezomib or 28 days after the last dose of pomalidomide, whichever is later
(Arm B)
For additional information see section 5.1 of the protocol
- Prior treatment with CAR-T therapy directed at any target.
- Any previous therapy that is targeted to BCMA.
- Ongoing toxicity from previous anticancer therapy that has not resolved to
baseline levels or to Grade 1 or less; except for alopecia.
- Subjects with Grade 1 peripheral neuropathy with pain or Grade 2 or higher
peripheral neuropathy will not be permitted to receive PVd as standard therapy
or bridging therapy; however, subject may receive DPd as standard therapy or
bridging therapy.
- Was vaccinated with live attenuated vaccines within 4 weeks prior to
randomization
- Subject received any antitumor therapy as specified in the protocol, prior to
randomization
- Active malignancies (ie, progressing or requiring treatment change in the last
24 months) other than the disease being treated under study. Refer to the
protocol for allowed exceptions.
- Plasma cell leukemia at the time of screening, Waldenström*s
macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or primary AL
amyloidosis.
- Contraindications or life-threatening allergies, hypersensitivity, or
intolerance to JNJ 68284528 or its excipients, including dimethylsulfoxide, or
to fludarabine, cyclophosphamide, tocilizumab, pomalidomide, dexamethasone.
* Subjects with contraindications or life-threatening allergies,
hypersensitivity, or
intolerance to daratumumab will not be permitted to receive DPd as standard
therapy or bridging therapy; however, subjects may receive PVd as standard
therapy or bridging therapy. Likewise, subjects with contraindications or
life-threatening allergies, hypersensitivity, or intolerance to bortezomib will
not be permitted to receive PVd as standard therapy or bridging therapy; but
may receive DPd as standard therapy or bridging therapy.
- Stroke or seizure within 6 months of signing ICF.
- Received either of the following:
* An allogenic stem cell transplant within 6 months before apheresis. Subjects
who received an allogeneic transplant must have stopped all immunosuppressive
medications for 6 weeks without signs of graft-versus-host disease. Subjects
with active graft-versus-host disease are excluded.
* An autologous stem cell transplantation <= 12 weeks before apheresis.
- Known active, or prior history of central nervous system (CNS) involvement or
exhibits clinical signs of meningeal involvement of MM.
For additional information, see section 5.2 of the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint:<br /><br>- progression free survival</p><br>
- Secondary Outcome Measures
Name Time Method <p>- define further responses per IMWG:<br /><br>* Rate of CR/sCR<br /><br>* Overall MRD negative rate<br /><br>* Rate of MRD negativity in subjects with CR/sCR at 12 months ±3 months*<br /><br>* Rate of sustained MRD negative status<br /><br>* OS<br /><br>* ORR<br /><br>* PFS on next line of therapy<br /><br><br /><br>- Incidence and severity of adverse events<br /><br>- PK and PD markers<br /><br>- Presence of anti-JNJ-68284528 antibodies<br /><br>- Change from baseline in health-related quality of life</p><br>