Clinical Trials /

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

NCT04700176

Description:

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).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Pro2020-0280
  • NCT ID: NCT04700176

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
DaratumumabDarzalexProgressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
PomalidomidePomalystProgressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
All-trans retinoic acidATRAProgressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)
DexamethasoneProgressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
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)
  • Daratumumab
  • Pomalidomide
  • All-trans retinoic acid
  • 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)
  • Daratumumab
  • Pomalidomide
  • All-trans retinoic acid
  • Dexamethasone

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (Cohort A)
Time Frame:12 Months
Safety Issue:
Description:To determine the ORR of the combination of Dara + Pom + Dex + ATRA in patients progressing on Dara + Len + Dex (Cohort A)

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hackensack Meridian Health

Last Updated

January 7, 2021