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

NCT04700176 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro2020-0280
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (9)

• Objective Response Rate (Cohort B)

  12 Months

• Rate of Stringent Complete Response

  12 Months

• Incidence of Treatment-Emergent Adverse Events

  12 Months

• Rate of Minimal Residual Disease Evaluation

  12 Months

• Time on Study (TOS)

  12 Months

Study Arms (2)

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)

Drug: Daratumumab; Drug: Pomalidomide; Drug: All-trans retinoic acid; Drug: Dexamethasone

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)

Drug: Daratumumab; Drug: Pomalidomide; Drug: All-trans retinoic acid; Drug: Dexamethasone

Interventions

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.

Also known as: Darzalex

Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A); Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)

Pomalidomide DRUG

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

Also known as: Pomalyst

Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A); Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)

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

Also known as: ATRA

Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A); Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)

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.

Also known as: Decadron

Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A); Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hackensack Meridian Health: lead
• Janssen, LP: collaborator

Study Sites (1)

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (19)

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  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; pomalidomide; Tretinoin; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

joshua.zenreich@hmhn.org

551-996-4248

Study Officials

• Noa Biran, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 7, 2021
• Study Start: May 2, 2022
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)