A Clinical Study of Subcutaneous Daratumumab Regimens in Combination with Bispecific T Cell Redirection Antibodies for the Treatment of Subjects with Multiple Myeloma

Phase 1

• Conditions: Multiple myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000330-19-NL
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-13
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 145

Inclusion Criteria

Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1. =18 years of age.
2. Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
3. Must have either of the following:
? Received at least 3 prior lines of therapy (see definition below) including a PI (=2 cycles or 2 months of treatment) and an IMiD (=2 cycles or 2 months of treatment) in any order during the treatment (except for subjects who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months).
- Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease was the best response to the line of therapy.
OR
? Disease that is double refractory to a PI and an IMiD. For subjects who have received more than 1 type of PI, the disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMiD, the disease must be refractory to the most recent one.
NOTE: Subject must have documented evidence of progressive disease based on investigator’s determination of response by the IMWG 2016 criteria as described by Kumar et al. on or within 12 months of their last line of therapy. 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 therapy afterwards are eligible.
NOTE: For subjects who are to be enrolled in a treatment combination that includes pomalidomide, prior IMiD therapy should include lenalidomide.
4. Measurable disease at screening as defined by any of the following:
? Serum monoclonal protein (M-protein)level =1.0 g/dL (in non-IgG myeloma, an M-protein level =0.5 g/dL);or
? Urine M-protein level =200 mg/24 hours; or
? Light chain multiple myeloma: Serum Ig free light chain (FLC) =10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
5. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose.
6. Clinical lab values as stated in the protocol
7. Women of childbearing potential must have a negative highly -sensitive serum ß human chorionic gonadotropin (ß-hCG) pregnancy test (<5 IU/mL) at screening and a negative urine or serum pregnancy test within 24 hours before the first dose of study drug and must agree to further serum or urine pregnancy tests during the study.
8. Women must be either of the following:
a. Not of childbearing potential b. Of childbearing potential and
– practicing true abstinence; or have a sole partner who is vasectomized;or practicing at least 1 highly effective user-independent method of contraception
Subject must agree to continue the above while receiving study drug and until 100 days after last dose. Women of childbearing potential must agree to
pregnancy testing (serum or urine) within 100 days after the last study drug administration.
Note: If a woman becomes of childbearing potential after start of the study the woman must comply with point (b.) as described above. A woman using oral contraceptives must use an additional contraceptive method in addition to the requirements listed above.
9. Men 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 th

Exclusion Criteria

Any potential participant who meets any of the following criteria will be excluded from participating in the study:
1. Treatment in the prior 90 days with an anti-CD38 therapy (eg, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy.
2. Prior antitumor therapy as follows, before the first dose of study drug:
• Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive medical device within 21 days or at least 5 half-lives, whichever is less.
• Monoclonal antibody treatment within 21 days (anti-CD38 treatment cannot be used within the prior 90 days
• Cytotoxic therapy within 21 days.
• PI therapy within 14 days.
• IMiD therapy within 7 days.
• Radiotherapy within 21 days. However, if the radiation portal covered =5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.
• Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified Tcells, NK cells) within 90 days
3. A cumulative dose of corticosteroids equivalent to =140 mg of prednisone within the 14-day period before the first dose of study drugs
4. Live, attenuated vaccine within 4 weeks prior to the first dose of study drug unless approved by sponsor.
5. Toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade =1 (except alopecia [any grade] or peripheral neuropathy Grade =3).
6. Stem cell transplantation:
• Subjects who received an allogeneic transplant must be off all immunosuppressive medications for >42 days without signs of graft-versus-host disease.
• Autologous stem cell transplantation =12 weeks before the first dose of study drug.
• An immunosuppressive drug (eg, cyclosporine, tacrolimus) within 28 days before the first dose of study drug.
7. Active central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required.
8. Active plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis.
9. Known to be seropositive for human immunodeficiency virus.
10. Seropositive for hepatitis B (defined by a positive test for hepatitisB surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative with antibodies to total hepatitis B core antigen [Anti-HBc]
with or without the presence of hepatitis B surface antibodies [Anti-HBs]) 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 (Anti-HBs 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.
11. Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing.
12. Either of the following:
• Chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) <50% of predicted normal. NOTE: FEV1 testing is required for subjects suspected of having COPD and subjects must be

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified