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NCT04700176 · REGISTRY CONDITION SEARCH

A Study of Daratumumab With Pomalidomide, Dexamethasone, and All-Transretinoic Acid in Patients With Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
TERMINATED
Registry last update
2025-02-25

The purpose of this study is to test the safety and efficacy of the study drug daratumumab, when given together with Pomalidomide, Dexamethasone, and All-Transretinoic Acid (ATRA).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Objective Response Rate (Cohort A)

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outcome · POSTED

Incidence of Adverse Events

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outcome · POSTED

Objective Response Rate (Cohort B)

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outcome · POSTED

Rate of Stringent Complete Response

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outcome · POSTED

Incidence of Treatment-Emergent Adverse Events

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outcome · POSTED

Rate of Minimal Residual Disease Evaluation

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outcome · POSTED

Time on Study (TOS)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Time To Progression (TTP)

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients with relapsed or refractory multiple myeloma who have progressed on the combination of Dara + Len + Dex (Cohort A) to be treated with a combination of Dara + Pom + Dex + ATRA (All-Transretinoic Acid)
    intervention Names
    1. Drug: Daratumumab
    2. Drug: Pomalidomide
    3. Drug: All-trans retinoic acid
    4. Drug: Dexamethasone
    label
    Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
    type
    EXPERIMENTAL
  2. description
    Patients with relapsed or refractory multiple myeloma who have progressed on the combination of Dara + Pom + Dex (Cohort B) to be treated with a combination of Dara + Pom + Dex + ATRA (All-Transretinoic Acid)
    intervention Names
    1. Drug: Daratumumab
    2. Drug: Pomalidomide
    3. Drug: All-trans retinoic acid
    4. Drug: Dexamethasone
    label
    Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
    2. Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)
    description
    During 28-day treatment cycles, patients will receive Dara 16 mg/kg intravenously (IV) at their current dose upon enrollment onto the study depending on their cycle. They will receive Dara depending on the cycle they are in. If they are on cycles 1-2 then they will receive Dara 16 mg/kg IV on days 1,8,15,22; if they are on cycles 3-6 they will receive Dara 16 mg/kg on days 1 and 15; and if they are on cycle 7 or beyond they will receive Dara 16 mg/kg on day 1.
    name
    Daratumumab
    other Names
    1. Darzalex
    type
    DRUG
  2. arm Group Labels
    1. Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
    2. Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)
    description
    Pomalidomide will be administered at the patient's currently tolerated dose (4,3, or 2 mg po daily) on days 1-21
    name
    Pomalidomide
    other Names
    1. Pomalyst
    type
    DRUG
  3. arm Group Labels
    1. Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
    2. Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)
    description
    ATRA will be administered in a divided dose of twice daily as an oral formulation at 45mg/m2/day for 3 days. The first administration of ATRA will be given in the morning, two days before the scheduled Dara infusion. The last administration of ATRA will be given in the evening of the day that Dara was administered
    name
    All-trans retinoic acid
    other Names
    1. ATRA
    type
    DRUG
  4. arm Group Labels
    1. Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
    2. Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)
    description
    Dexamethasone will be administered at 40 mg once weekly on days 1,8,15 for patients 75 years old and younger and at 20 mg once weekly on days 1,8,15 for patients older than 75.
    name
    Dexamethasone
    other Names
    1. Decadron
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
1
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Len + Dex (Cohort A)
    measure
    Objective Response Rate (Cohort A)
    time Frame
    12 Months
  2. description
    Incidence of Adverse Events in the combination of Dara + Pom + Dex + ATRA using CTCAE V5 criteria.
    measure
    Incidence of Adverse Events
    time Frame
    12 Months
secondary Outcomes
  1. description
    To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Pom + Dex
    measure
    Objective Response Rate (Cohort B)
    time Frame
    12 Months
  2. description
    To determine the best stringent complete response (sCR)/CR/near CR (nCR) and \>/= very good partial response (VGPR) rates.
    measure
    Rate of Stringent Complete Response
    time Frame
    12 Months
  3. description
    To define the toxicity using CTCAE V5 criteria.
    measure
    Incidence of Treatment-Emergent Adverse Events
    time Frame
    12 Months
  4. description
    To evaluate the status of minimal residual disease (MRD) in patients who achieve sCR, CR, or nCR.
    measure
    Rate of Minimal Residual Disease Evaluation
    time Frame
    12 Months
  5. description
    Duration from start of study treatment to end of study
    measure
    Time on Study (TOS)
    time Frame
    12 Months
  6. description
    Duration from treatment response to progression
    measure
    Duration of Response (DOR)
    time Frame
    12 Months
  7. description
    Duration from start of study treatment to progression
    measure
    Time To Progression (TTP)
    time Frame
    12 Months
  8. description
    Duration from start of study treatment to PD or death \[regardless of cause\], whichever comes first
    measure
    Progression-Free Survival (PFS)
    time Frame
    12 Months
  9. description
    Duration from start of study treatment to death
    measure
    Overall Survival (OS)
    time Frame
    12 Months
Full study description
brief Summary
The purpose of this study is to test the safety and efficacy of the study drug daratumumab, when given together with Pomalidomide, Dexamethasone, and All-Transretinoic Acid (ATRA).
detailed Description
This is a multi-institution phase II study of ATRA in combination with fixed dose Daratumumab, Pomalidomide and Dex for a total of 33 patients in patients with relapsed multiple myeloma who have progressed on the combination of Dara + Len + Dex. There will also be an exploratory cohort with an additional 10 patients who have progressed on the combination of Dara + Pom + Dex.
Source references
references
  1. citation
    Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, Haessler J, Feather J, Hoering A, Moreau P, LeLeu X, Hulin C, Klein SK, Sonneveld P, Siegel D, Blade J, Goldschmidt H, Jagannath S, Miguel JS, Orlowski R, Palumbo A, Sezer O, Rajkumar SV, Durie BG; International Myeloma Working Group. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan;26(1):149-57. doi: 10.1038/leu.2011.196. Epub 2011 Jul 29.
    pmid
    21799510
    type
    BACKGROUND
  2. citation
    Lee HC. Structure and enzymatic functions of human CD38. Mol Med. 2006 Nov-Dec;12(11-12):317-23. doi: 10.2119/2006-00086.Lee.
    pmid
    17380198
    type
    BACKGROUND
  3. citation
    Chillemi A, Zaccarello G, Quarona V, Ferracin M, Ghimenti C, Massaia M, Horenstein AL, Malavasi F. Anti-CD38 antibody therapy: windows of opportunity yielded by the functional characteristics of the target molecule. Mol Med. 2013 May 20;19(1):99-108. doi: 10.2119/molmed.2013.00009.
    pmid
    23615966
    type
    BACKGROUND
  4. citation
    Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.
    pmid
    27705267
    type
    BACKGROUND
  5. citation
    Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Weiss BM, Krishnan A, Lentzsch S, Comenzo R, Wang J, Nottage K, Chiu C, Khokhar NZ, Ahmadi T, Lonial S. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017 Aug 24;130(8):974-981. doi: 10.1182/blood-2017-05-785246. Epub 2017 Jun 21.
    pmid
    28637662
    type
    BACKGROUND
  6. citation
    Nijhof IS, Groen RW, Lokhorst HM, van Kessel B, Bloem AC, van Velzen J, de Jong-Korlaar R, Yuan H, Noort WA, Klein SK, Martens AC, Doshi P, Sasser K, Mutis T, van de Donk NW. Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab. Leukemia. 2015 Oct;29(10):2039-49. doi: 10.1038/leu.2015.123. Epub 2015 May 15.
    pmid
    25975191
    type
    BACKGROUND
  7. citation
    Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016 Aug 18;128(7):959-70. doi: 10.1182/blood-2016-03-703439. Epub 2016 Jun 15.
    pmid
    27307294
    type
    BACKGROUND
  8. citation
    Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008 Aug 29;321(5893):1218-21. doi: 10.1126/science.1158799. Epub 2008 Jul 31.
    pmid
    18669821
    type
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  9. citation
    Wichterle H, Lieberam I, Porter JA, Jessell TM. Directed differentiation of embryonic stem cells into motor neurons. Cell. 2002 Aug 9;110(3):385-97. doi: 10.1016/s0092-8674(02)00835-8.
    pmid
    12176325
    type
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  10. citation
    Collins SJ. The role of retinoids and retinoic acid receptors in normal hematopoiesis. Leukemia. 2002 Oct;16(10):1896-905. doi: 10.1038/sj.leu.2402718.
    pmid
    12357341
    type
    BACKGROUND
  11. citation
    Kantarjian HM, Keating MJ, Walters RS, Estey EH, McCredie KB, Smith TL, Dalton WT Jr, Cork A, Trujillo JM, Freireich EJ. Acute promyelocytic leukemia. M.D. Anderson Hospital experience. Am J Med. 1986 May;80(5):789-97. doi: 10.1016/0002-9343(86)90617-0.
    pmid
    3458366
    type
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  12. citation
    Cordonnier C, Vernant JP, Brun B, Heilmann MG, Kuentz M, Bierling P, Farcet JP, Rodet M, Duedari N, Imbert M, et al. Acute promyelocytic leukemia in 57 previously untreated patients. Cancer. 1985 Jan 1;55(1):18-25. doi: 10.1002/1097-0142(19850101)55:13.0.co;2-b.
    pmid
    3855265
    type
    BACKGROUND
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice