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

February 21, 2025 updated by: Hackensack Meridian Health

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • John Theurer Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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)
Drug: 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.
Other Names:
  • Darzalex
Drug: Pomalidomide
Pomalidomide will be administered at the patient's currently tolerated dose (4,3, or 2 mg po daily) on days 1-21
Other Names:
  • Pomalyst
Drug: 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
Other Names:
  • ATRA
Drug: 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.
Other Names:
  • Decadron
Experimental: 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)
Drug: 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.
Other Names:
  • Darzalex
Drug: Pomalidomide
Pomalidomide will be administered at the patient's currently tolerated dose (4,3, or 2 mg po daily) on days 1-21
Other Names:
  • Pomalyst
Drug: 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
Other Names:
  • ATRA
Drug: 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.
Other Names:
  • Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (Cohort A)
Time Frame: 12 Months
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
Time Frame: 12 Months
Incidence of Adverse Events in the combination of Dara + Pom + Dex + ATRA using CTCAE V5 criteria.
12 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (Cohort B)
Time Frame: 12 Months
To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Pom + Dex
12 Months
Incidence of Treatment-Emergent Adverse Events
Time Frame: 12 Months
To define the toxicity using CTCAE V5 criteria.
12 Months
Time on Study (TOS)
Time Frame: 12 Months
Duration from start of study treatment to end of study
12 Months
Duration of Response (DOR)
Time Frame: 12 Months
Duration from treatment response to progression
12 Months
Time To Progression (TTP)
Time Frame: 12 Months
Duration from start of study treatment to progression
12 Months
Progression-Free Survival (PFS)
Time Frame: 12 Months
Duration from start of study treatment to PD or death [regardless of cause], whichever comes first
12 Months
Overall Survival (OS)
Time Frame: 12 Months
Duration from start of study treatment to death
12 Months
Rate of Stringent Complete Response
Time Frame: 12 Months
To determine the best stringent complete response (sCR)/CR/near CR (nCR) and >/= very good partial response (VGPR) rates.
12 Months
Rate of Minimal Residual Disease Evaluation
Time Frame: 12 Months
To evaluate the status of minimal residual disease (MRD) in patients who achieve sCR, CR, or nCR.
12 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Collaborators

Janssen, LP

Investigators

  • Principal Investigator: Noa Biran, MD, Hackensack Meridian Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2022

Primary Completion (Actual)

November 15, 2023

Study Completion (Actual)

November 15, 2023

Study Registration Dates

First Submitted

January 4, 2021

First Submitted That Met QC Criteria

January 5, 2021

First Posted (Actual)

January 7, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 21, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro2020-0280

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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