Not provided
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Low Accrual
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| Name | Class |
|---|---|
| Janssen, LP | INDUSTRY |
Not provided
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A) | Experimental | 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) |
|
| Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B) | Experimental | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daratumumab | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 12 Months |
| Incidence of Adverse Events | Incidence of Adverse Events in the combination of Dara + Pom + Dex + ATRA using CTCAE V5 criteria. | 12 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (Cohort B) | To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Pom + Dex | 12 Months |
| Rate of Stringent Complete Response |
Not provided
Inclusion Criteria:
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:
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:
Prior to first dose of study drug, a woman must be either:
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).
Exclusion Criteria:
Not provided
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| Name | Affiliation | Role |
|---|---|---|
| Noa Biran, MD | Hackensack Meridian Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| John Theurer Cancer Center | Hackensack | New Jersey | 07601 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21799510 | Background | 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. | |
| 17380198 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
| FG001 | Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
No patients enrolled in Cohort B
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | No patients enrolled in Cohort B | Posted | Count of Participants | Participants | 12 Months |
|
Adverse events are captured from time of consent through 30 days after the last dose of study drug, approximately 8 months
Cohort B was not enrolled
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | Investigations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Brain Fogginess | Nervous system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joshua Zenreich | Hackensack Meridian Health | 551-996-4248 | joshua.zenreich@hmhn.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 29, 2022 | Jan 17, 2025 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C556306 | daratumumab |
| C467566 | pomalidomide |
| D014212 | Tretinoin |
| D003907 | Dexamethasone |
| D002123 | Calcium Dobesilate |
| ID | Term |
|---|---|
| D014801 | Vitamin A |
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Pomalidomide | Drug | 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 acid | Drug | 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 |
|
|
| Dexamethasone | Drug | 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. |
|
|
To determine the best stringent complete response (sCR)/CR/near CR (nCR) and >/= very good partial response (VGPR) rates.
| 12 Months |
| Incidence of Treatment-Emergent Adverse Events | To define the toxicity using CTCAE V5 criteria. | 12 Months |
| Rate of Minimal Residual Disease Evaluation | To evaluate the status of minimal residual disease (MRD) in patients who achieve sCR, CR, or nCR. | 12 Months |
| Time on Study (TOS) | Duration from start of study treatment to end of study | 12 Months |
| Duration of Response (DOR) | Duration from treatment response to progression | 12 Months |
| Time To Progression (TTP) | Duration from start of study treatment to progression | 12 Months |
| Progression-Free Survival (PFS) | Duration from start of study treatment to PD or death [regardless of cause], whichever comes first | 12 Months |
| Overall Survival (OS) | Duration from start of study treatment to death | 12 Months |
| Background |
| 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. |
| 23615966 | Background | 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. |
| 27705267 | Background | 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. |
| 28637662 | Background | 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. |
| 25975191 | Background | 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. |
| 27307294 | Background | 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. |
| 18669821 | Background | 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. |
| 12176325 | Background | 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. |
| 12357341 | Background | 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. |
| 3458366 | Background | 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. |
| 3855265 | Background | 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. |
| 1732003 | Background | Tallman MS, Kwaan HC. Reassessing the hemostatic disorder associated with acute promyelocytic leukemia. Blood. 1992 Feb 1;79(3):543-53. No abstract available. |
| 2224120 | Background | 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. |
| 9321529 | Background | 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. |
| 7949175 | Background | Ogata A, Nishimoto N, Shima Y, Yoshizaki K, Kishimoto T. Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction. Blood. 1994 Nov 1;84(9):3040-6. |
| Background | Siegel D, Niesvizky R, Miller WH Jr, Busquets X, Kumar R, MIchaeli J: All trans retinoic acid (ATRA) and interferon alfa (IFNa) synergistically inhibit myeloma cell growth and induce retinoic acid receptor alfa (RARa) expression. Blood 80:121a:1992 (abstr, supple 1). |
| 7780162 | Background | Musto P, Falcone A, Sajeva MR, D'Arena G, Bonini A, Carotenuto M. All-trans retinoic acid for advanced multiple myeloma. Blood. 1995 Jun 15;85(12):3769-70. No abstract available. |
| 34625791 | Background | Frerichs KA, Minnema MC, Levin MD, Broijl A, Bos GMJ, Kersten MJ, Mutis T, Verkleij CPM, Nijhof IS, Maas-Bosman PWC, Klein SK, Zweegman S, Sonneveld P, van de Donk NWCJ. Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma. Blood Adv. 2021 Dec 14;5(23):5128-5139. doi: 10.1182/bloodadvances.2021005220. |
| BG001 | Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. |
|
|
| Primary | Incidence of Adverse Events | Incidence of Adverse Events in the combination of Dara + Pom + Dex + ATRA using CTCAE V5 criteria. | No participants enrolled in cohort B | Posted | Count of Participants | Participants | 12 Months |
|
|
|
| Secondary | Objective Response Rate (Cohort B) | To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Pom + Dex | No participants enrolled in cohort B | Posted | 12 Months |
|
|
| Secondary | Rate of Stringent Complete Response | To determine the best stringent complete response (sCR)/CR/near CR (nCR) and >/= very good partial response (VGPR) rates. | No participants enrolled in cohort B | Posted | Count of Participants | Participants | 12 Months |
|
|
|
| Secondary | Incidence of Treatment-Emergent Adverse Events | To define the toxicity using CTCAE V5 criteria. | No participants enrolled in cohort B | Posted | Count of Participants | Participants | 12 Months |
|
|
|
| Secondary | Rate of Minimal Residual Disease Evaluation | To evaluate the status of minimal residual disease (MRD) in patients who achieve sCR, CR, or nCR. | No participants enrolled in cohort B | Posted | Count of Participants | Participants | 12 Months |
|
|
|
| Secondary | Time on Study (TOS) | Duration from start of study treatment to end of study | Patient withdrew consent to follow up at time of progression. No participants enrolled in cohort B | Posted | Number | Months | 12 Months |
|
|
|
| Secondary | Duration of Response (DOR) | Duration from treatment response to progression | No participants enrolled in cohort B | Posted | Number | Months | 12 Months |
|
|
|
| Secondary | Time To Progression (TTP) | Duration from start of study treatment to progression | No participants enrolled in cohort B | Posted | Number | Months | 12 Months |
|
|
|
| Secondary | Progression-Free Survival (PFS) | Duration from start of study treatment to PD or death [regardless of cause], whichever comes first | No participants enrolled in cohort B | Posted | Number | Months | 12 Months |
|
|
|
| Secondary | Overall Survival (OS) | Duration from start of study treatment to death | Patient withdrew consent to follow up at time of progression | Posted | 12 Months |
|
|
| 0 |
| 1 |
| 1 |
| 1 |
| 1 |
| 1 |
| EG001 | Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B) | 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) Daratumumab: 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. Pomalidomide: 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 acid: 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 Dexamethasone: 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. | 0 | 0 | 0 | 0 | 0 | 0 |
| Febrile Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| RSV | Infections and infestations | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation Intermittent | Gastrointestinal disorders | Systematic Assessment |
|
| COVID-19 | Infections and infestations | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Productive Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| RSV | Infections and infestations | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Urinary Frequency | Renal and urinary disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D004224 | Diterpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |