A Phase 1b-2, Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA in Subjects with Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple Myeloma / symptomatic plasma cell disorder10018865
- Registration Number
- NL-OMON48195
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Trial never started
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 6
1. 18 years of age.
2. Documented diagnosis of multiple myeloma according to IMWG diagnostic
criteria.
3. Measurable disease at Screening as defined by any of the following:
- Serum monoclonal paraprotein (M-protein) level greater than or equal to 1.0
g/dL or urine M-protein level greater than or equal to 200 mg/24 hours or
- Light chain multiple myeloma without measurable disease in the serum or the
urine: Serum immunoglobulin free light chain greater than or equal to 10 mg/dL
and abnormal serum immunoglobulin kappa lambda free light chain ratio.
4. Received at least 3 prior multiple myeloma treatment regimens or are double
refractory to an IMiD and PI (refractory multiple myeloma as defined by IMWG
consensus criteria). Note: induction with or without hematopoietic stem cell
transplant and with or without maintenance therapy is considered a single
regimen. Undergone at least 1 complete cycle of treatment for each regimen,
unless PD was the best response to the regimen.
5. Received as part of previous therapy a PI, an IMiD, and an anti-CD38
antibody (prior exposure can be from different monotherapy or combination
regimens).
6. Subject must have documented evidence of progressive disease based on
investigator*s determination of response by the IMWG criteria on or within 12
months of their last regimen. Confirmation may be from either central or local
testing. Also, subjects with documented evidence of progressive disease (as
above) within the previous 6 months and who are refractory or non-responsive to
their most recent line of treatment afterwards are eligible.
7. ECOG Performance Status grade of 0 or 1.
8. Clinical laboratory values as specified in the protocol.
9. Women of childbearing potential must have a negative pregnancy test at
screening and prior to the first dose of cyclophosphamide and fludarabine using
a highly sensitive serum pregnancy test (β human chorionic gonadotropin [β-
hCG]).
10. When a woman is of childbearing potential the following is required:
-Subject must agree to practice a highly effective method of contraception
(failure rate of <1% per year when used consistently and correctly) and agree
to remain on a highly effective method of contraception from the time of
signing the informed consent form (ICF) until at least 100 days after receiving
a JNJ-68284528 infusion.
In addition to the highly effective method of contraception a man:
-Who is sexually active with a woman of childbearing potential must agree to
use a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository) from the time of signing the ICF until at
least 100 days after receiving a JNJ-68284528 infusion.
- Who is sexually active with a woman who is pregnant must use a condom.
Women and men must agree not to donate eggs (ova, oocytes) or sperm,
respectively, during the study and for 100 days after the last dose of study
treatment.
11. Subject must sign an ICF indicating that he or she understands the purpose
of and procedures required for the study and is willing to participate in the
study. Consent is to be obtained prior to the initiation of any study-related
tests or procedures that are not part of standard-of-care for the subject*s
disease.
12. Willing and able to adhere to the prohibitions and restrictions specified <b
1. Prior treatment with CAR-T therapy directed at any target.
2. Any therapy that is targeted to BCMA.
3. Diagnosed or treated for invasive malignancy other than multiple myeloma,
except:
-Malignancy treated with curative intent and with no known active disease
present for greater than or equal to 2 years before enrollment or
-Adequately treated non-melanoma skin cancer without evidence of disease.
4. Prior antitumor therapy as follows, prior to apheresis:
-Targeted therapy, epigenetic therapy, or treatment with an investigational
drug or used an invasive investigational medical device within 14 days or at
least 5 half lives, whichever is less.
-Monoclonal antibody treatment for multiple myeloma within 21 days.
-Cytotoxic therapy within 14 days.
-Proteasome inhibitor therapy within 14 days.
-Immunomodulatory agent therapy within 7 days.
-Radiotherapy within 14 days. However, if the radiation portal covered less
than or equal to 5% of the bone marrow reserve, the subject is eligible
irrespective of the end date of radiotherapy.
5. Toxicity from previous anticancer therapy must resolve to baseline levels or
to Grade 1 or less except for alopecia or peripheral neuropathy.
6. The following cardiac conditions:
-New York Heart Association (NYHA) stage III or IV congestive heart failure.
-Myocardial infarction or coronary artery bypass graft (CABG) less than or
equal to 6 months prior to enrollment.
-History of clinically significant ventricular arrhythmia or unexplained
syncope, not believed to be vasovagal in nature or due to dehydration.
-History of severe non-ischemic cardiomyopathy.
-Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or
multiple-gated acquisition (MUGA) scan (performed less than or equal to 8 weeks
of apheresis).
7. Received a cumulative dose of corticosteroids equivalent to >=70 mg of
prednisone within the 7 days prior to apheresis.
8. Received either of the following:
-An allogenic stem cell transplant within 6 months before apheresis. Subjects
who received an allogeneic transplant must be off all immunosuppressive
medications for 6 weeks without signs of graft-versus-host disease (GVHD).
-An autologous stem cell transplant less than or equal to 12 weeks before
apheresis.
9. Known active, or prior history of central nervous system (CNS) involvement
or exhibits clinical signs of meningeal involvement of multiple myeloma.
10. Stroke or seizure within 6 months of signing ICF.
11. Plasma cell leukemia at the time of screening (>2,0 x 10^9/L plasma cells
by standard differential), Waldenström*s macroglobulinemia, POEMS syndrome
(polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin
changes), or primary AL amyloidosis.
12. Seropositive for human immunodeficiency virus (HIV).
13. Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis.
14. Hepatitis B infection as defined in the protocol. In the event the
infection status is unclear, quantitative levels are necessary to determine the
infection status.
15. Hepatitis C infection defined as (anti-hepatitis C virus [HCV] antibody
positive or HCV-RNA positive) or known to have a history of hepatitis C. For
subjects with known history of HCV infection, confirmation of sustained
virologic response [SVR] is required for study eligibility, defi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method