Inclusion Criteria:
1. Documented multiple myeloma. 2. For cohort A, patients must have been previously exposed to Dara+Len+Dex and must have
achieved at least stable disease to this combination.
3. For cohort B, patients must have been exposed to Dara + Pom + Dex and must have
achieved at least stable disease to this combination.
4. Histologically confirmed and relapsed multiple myeloma with measurable disease,
defined by at least one of the following:
1. Serum monoclonal protein ≥0.5 g/dL;
2. Monoclonal protein in the urine on 24-hour electrophoresis ≥200 mg;
3. Serum immunoglobulin free light chain (FLC) ≥10 mg/dL (100 mg/L) provided serum
FLC ratio is abnormal;
4. New of progressing biopsy proven plasmacytoma on exam or imaging; or. 5. Bone marrow plasma cells ≥20%;
5. Cycle 1 day 1 of study treatment must be within 3 months of last exposure to
Daratumumab.
6. Life expectancy >3 months. 7. ECOG PS 0-2. 8. Age ≥18. 9. Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac
function based on the last assessment performed within the Screening Period, defined
as:
1. Absolute neutrophil count (ANC) ≥1,000/μL;
2. Platelet count ≥50,000/μL, (≥30,000/μL if bone marrow plasma cells are ≥50% of
cellularity);
3. Hemoglobin ≥7.5g/dL;
4. Creatinine clearance ≥60 mL/min (assessed as glomerular filtration rate using the
Cockcroft-Gault formula);
5. Alanine aminotransferase or aspartate aminotransferase <3 x upper limit of normal
(ULN);
6. Total bilirubin <2 x ULN (except for patients with Gilbert's syndrome confirmed
by UGT1A1 mutation);
7. Left ventricular ejection fraction ≥50% as assessed by echocardiography or
multi-gated acquisition (MUGA) scan; and. 8. Must have a minimum level of pulmonary reserve defined as Grade <2 dyspnea and
pulse oxygenation ≥92% on room air;
10. Prior to first dose of study drug, a woman must be either:
- - Not of childbearing potential: premenarchal; postmenopausal (>45 years of age
with amenorrhea for at least 12 months or any age with amenorrhea for at least 6
months and a serum follicle stimulating hormone level >40 IU/L or mIU/mL]);
permanently sterilized (eg, bilateral tubal occlusion [which includes tubal
ligation procedures as consistent with local regulations], hysterectomy,
bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of
pregnancy.
- - Of childbearing potential and practicing a highly effective method of birth
control for 4 weeks before initiating study treatment that is consistent with
local regulations regarding the use of birth control methods for subjects
participating in clinical studies: e.g., established use of oral, injected or
implanted hormonal methods of contraception; placement of an intrauterine device
or intrauterine system; barrier methods: condom with spermicidal
foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/suppository; male partner
sterilization (the vasectomized partner should be the sole partner for that
subject); true abstinence (when this is in line with the preferred and usual
lifestyle of the subject) Note: If the childbearing potential changes after start
of the study (e.g., woman who is not heterosexually active becomes active,
premenarchal woman experiences menarche)
- a woman must begin a highly effective method of birth control, as described
above.
11. A woman of childbearing potential must have 2 negative serum (β human chorionic
gonadotropin) or urine pregnancy tests during screening, the first one within 28 days
prior to the first dose of study drug and the second within 24 hours prior to the
first dose of study drug.
12. A man who is sexually active with a woman of childbearing potential and has not had a
vasectomy must agree to use a barrier method of birth control e.g., either condom with
spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
must also not donate sperm during the study and for 3 months after receiving the last
dose of study drug.
13. Subjects must be willing and able to adhere to the prohibitions and restrictions
specified in this protocol and referenced in the informed consent form (ICF).
Exclusion Criteria:
1. Major concurrent illness or organ dysfunction. 2. Active GVHD requiring systemic corticosteroids in a subject who previously received
allogeneic-SCT.
3. Cord compression or CNS involvement. 4. Recent/Prior active malignancy requiring active therapy 2 years prior to enrollment
excluding non-melanoma skin cancer.
5. Prior life-threatening hypersensitivity to daratumumab or an IMiD. 6. Plasma cell leukemia. 7. Pregnant or lactating females. 8. Men donating sperm during study. 9. Seropositive for human immunodeficiency virus (HIV)
10. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface
antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg
negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or
antibodies to hepatitis B surface antigen [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. Seropositive for hepatitis C (except in the setting of a sustained virologic response
[SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
12. Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1
second (FEV1) less than 50% of predicted normal
