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Multiple MyelomaPhase 2NCT04700176

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

A Phase 2 study testing Daratumumab, Pomalidomide and All-trans retinoic acid in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab, Pomalidomide and All-trans retinoic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
2 May 2022to 15 Nov 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented multiple myeloma
  • For cohort A, patients must have been previously exposed to Dara+Len+Dex and must have achieved at least stable disease to this combination.
  • For cohort B, patients must have been exposed to Dara + Pom + Dex and must have achieved at least stable disease to this combination.
  • Histologically confirmed and relapsed multiple myeloma with measurable disease, defined by at least one of the following:
  • Serum monoclonal protein ≥0.5 g/dL;
  • Monoclonal protein in the urine on 24-hour electrophoresis ≥200 mg;
Show all 29Show fewer
  • Serum immunoglobulin free light chain (FLC) ≥10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal;
  • New of progressing biopsy proven plasmacytoma on exam or imaging; or
  • Bone marrow plasma cells ≥20%;
  • Cycle 1 day 1 of study treatment must be within 3 months of last exposure to Daratumumab.
  • Life expectancy >3 months
  • ECOG PS 0-2
  • Age ≥18
  • Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within the Screening Period, defined as:
  • Absolute neutrophil count (ANC) ≥1,000/μL;
  • Platelet count ≥50,000/μL, (≥30,000/μL if bone marrow plasma cells are ≥50% of cellularity);
  • Hemoglobin ≥7.5g/dL;
  • Creatinine clearance ≥60 mL/min (assessed as glomerular filtration rate using the Cockcroft-Gault formula);
  • Alanine aminotransferase or aspartate aminotransferase <3 x upper limit of normal (ULN);
  • Total bilirubin <2 x ULN (except for patients with Gilbert's syndrome confirmed by UGT1A1 mutation);
  • Left ventricular ejection fraction ≥50% as assessed by echocardiography or multi-gated acquisition (MUGA) scan; and
  • Must have a minimum level of pulmonary reserve defined as Grade <2 dyspnea and pulse oxygenation ≥92% on room air;
  • 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.
  • 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.
  • 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.
  • 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).

Who cannot join

  • Major concurrent illness or organ dysfunction
  • Active GVHD requiring systemic corticosteroids in a subject who previously received allogeneic-SCT.
  • Cord compression or CNS involvement
  • Recent/Prior active malignancy requiring active therapy 2 years prior to enrollment excluding non-melanoma skin cancer.
  • Prior life-threatening hypersensitivity to daratumumab or an IMiD
  • Plasma cell leukemia
Show all 12Show fewer
  • Pregnant or lactating females
  • Men donating sperm during study
  • Seropositive for human immunodeficiency virus (HIV)
  • 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
  • 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)
  • Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal

Trial locations and contacts

1 site in 1 country.

United States1 site

  • John Theurer Cancer Center

    Hackensack, New Jersey, 07601

Other trials in United States

About this study

Official title: A Multi-Center Phase 2 Study of Daratumumab With Pomalidomide and Dexamethasone in Combination With All-Transretinoic Acid in Patients With Multiple Myeloma Previously Exposed to Daratumumab-Based Regimens

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).

Read the 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.

Being tested
Daratumumab, Pomalidomide, All-trans retinoic acid, Dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DaratumumabDrug

    Also called Darzalex

    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.

  • PomalidomideDrug

    Also called Pomalyst

    Pomalidomide will be administered at the patient's currently tolerated dose (4,3, or 2 mg po daily) on days 1-21

  • All-trans retinoic acidDrug

    Also called ATRA

    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

  • DexamethasoneDrug

    Also called Decadron

    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.

Study groups in NCT04700176
Study groupRoleWhat they receive
Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)ExperimentalPatients 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)
Receives: Drug: Daratumumab; Drug: Pomalidomide; Drug: All-trans retinoic acid; Drug: Dexamethasone
Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)ExperimentalPatients 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)
Receives: Drug: Daratumumab; Drug: Pomalidomide; Drug: All-trans retinoic acid; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (Cohort A)

    To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Len + Dex (Cohort A)

    Measured: 12 Months

  2. Incidence of Adverse Events

    Incidence of Adverse Events in the combination of Dara + Pom + Dex + ATRA using CTCAE V5 criteria.

    Measured: 12 Months

Secondary outcomes (9)

  1. Objective Response Rate (Cohort B)

    To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Pom + Dex

    Measured: 12 Months

  2. Rate of Stringent Complete Response

    To determine the best stringent complete response (sCR)/CR/near CR (nCR) and >/= very good partial response (VGPR) rates.

    Measured: 12 Months

  3. Incidence of Treatment-Emergent Adverse Events

    To define the toxicity using CTCAE V5 criteria.

    Measured: 12 Months

  4. Rate of Minimal Residual Disease Evaluation

    To evaluate the status of minimal residual disease (MRD) in patients who achieve sCR, CR, or nCR.

    Measured: 12 Months

  5. Time on Study (TOS)

    Duration from start of study treatment to end of study

    Measured: 12 Months

  6. Duration of Response (DOR)

    Duration from treatment response to progression

    Measured: 12 Months

  7. Time To Progression (TTP)

    Duration from start of study treatment to progression

    Measured: 12 Months

  8. Progression-Free Survival (PFS)

    Duration from start of study treatment to PD or death [regardless of cause], whichever comes first

    Measured: 12 Months

  9. Overall Survival (OS)

    Duration from start of study treatment to death

    Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jan 2021
  2. Study start2 May 2022
  3. Primary completion15 Nov 2023
  4. Study completion15 Nov 2023

Why it stopped: Low Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04700176
Sponsor's protocol ID
Pro2020-0280
Status last verified
Feb 2025
First submitted
4 Jan 2021
Last updated
25 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 21799510

  • 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.

    PubMed 17380198

  • 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.

    PubMed 23615966

  • 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.

    PubMed 27705267

  • 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.

    PubMed 28637662

  • 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.

    PubMed 25975191

  • 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.

    PubMed 27307294

  • 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.

    PubMed 18669821

  • 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.

    PubMed 12176325

  • 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.

    PubMed 12357341

  • 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.

    PubMed 3458366

  • 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.

    PubMed 3855265

  • Tallman MS, Kwaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood. 1992 Feb 1;79(3):543-53. No abstract available.

    PubMed 1732003

  • Chomienne C, Ballerini P, Balitrand N, Daniel MT, Fenaux P, Castaigne S, Degos L. All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. Blood. 1990 Nov 1;76(9):1710-7.

    PubMed 2224120

  • Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997 Oct 9;337(15):1021-8. doi: 10.1056/NEJM199710093371501.

    PubMed 9321529

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Pomalidomide and All-trans retinoic acid in people with Multiple Myeloma, run by Hackensack Meridian Health at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (Cohort A) (time frame: 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04700176, which also lists 19 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.

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