Clinical Trials /

Daratumumab, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

NCT03841565

Description:

This phase II trial studies how well daratumumab, pomalidomide, and dexamethasone work in treating patients with multiple myeloma that has come back (relapsed). Immunotherapy with daratumumab may induce changes in body?s immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab with dexamethasone and pomalidomide may work bettering in treating patient compared to dexamethasone and pomalidomide alone.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
  • Official Title: Phase II Trial of Daratumumab Retreatment in Patients With Relapsed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: ACCRU-MY-1601
  • SECONDARY ID: NCI-2019-00386
  • SECONDARY ID: ACCRU-MY-1601
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03841565

Conditions

  • Recurrent Plasma Cell Myeloma

Interventions

DrugSynonymsArms
DaratumumabAnti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Treatment (pomalidomide, daratumumab, dexamethasone)
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDexTreatment (pomalidomide, daratumumab, dexamethasone)
Pomalidomide4-Aminothalidomide, Actimid, CC-4047, Imnovid, PomalystTreatment (pomalidomide, daratumumab, dexamethasone)

Purpose

This phase II trial studies how well daratumumab, pomalidomide, and dexamethasone work in treating patients with multiple myeloma that has come back (relapsed). Immunotherapy with daratumumab may induce changes in body?s immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab with dexamethasone and pomalidomide may work bettering in treating patient compared to dexamethasone and pomalidomide alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the overall response rate (partial response [PR], very good partial response
      [VGPR], complete response [CR], or stringent complete response [sCR]) of daratumumab
      retreatment in combination with pomalidomide and dexamethasone (DPd) in patients with
      relapsed refractory multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To assess progression free survival and overall survival associated with retreatment with
      daratumumab in combination with pomalidomide and dexamethasone (DPd) in patients with
      relapsed and refractory multiple myeloma.

      II. To determine the toxicities associated with retreatment with daratumumab in combination
      with pomalidomide and dexamethasone (DPd) .

      OUTLINE:

      Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21 and daratumumab
      intravenously (IV) on days 1, 8, 15, and 22 of cycles 1-2, days 1-15 of cycles 3-6, and day 1
      of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 of
      cycles 1-12. Cycles every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for every 3 months until
      subsequent treatment or progressive disease, then every 6 months for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pomalidomide, daratumumab, dexamethasone)ExperimentalPatients receive pomalidomide PO QD on days 1-21 and daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, days 1-15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Cycles every 28 days in the absence of disease progression or unacceptable toxicity.
  • Daratumumab
  • Dexamethasone
  • Pomalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min
             (obtained =< 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
             registration)

          -  Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)

          -  Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with
             Gilbert?s syndrome) (obtained =< 14 days prior to registration)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
             (obtained =< 14 days prior to registration)

          -  Measurable disease of multiple myeloma as defined by at least ONE of the following:

               -  Serum monoclonal protein >= 1.0 g/dL

               -  >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

               -  Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio

               -  Bone marrow >= 30% plasma cells

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  Relapsed multiple myeloma (MM) requiring treatment who have previously received a
             daratumumab alone or in a daratumumab containing combination and

               -  Had at least a partial response to therapy, and had disease progression on or
                  within 60 days of discontinuation

               -  At least 3 months should have elapsed since last exposure to daratumumab

               -  Patients must have been previously exposed to both a proteasome inhibitor and an
                  immunomodulatory imide drug (IMiD)

                    -  Examples of proteasome inhibitors:

                         -  Bortezomib, carfilzomib, ixazomib, marizomib, oprozomib

                    -  Examples of IMiD?s:

                         -  Thalidomide, lenalidomide, pomalidomide

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Willing to follow strict birth control measures

               -  Female patients: If they are of childbearing potential, agree to one of the
                  following:

                    -  Practice 2 effective methods of contraception, at the same time, from the
                       time of signing the informed consent form through 90 days after the last
                       dose of study drug, AND must also adhere to the guidelines of any
                       treatment-specific pregnancy prevention program, if applicable, OR

                    -  Agree to practice true abstinence when this is in line with the preferred
                       and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar,
                       ovulation, symptothermal, post-ovulation methods] and withdrawal are not
                       acceptable methods of contraception.)

               -  Male patients: even if surgically sterilized (i.e., status post-vasectomy), must
                  agree to one of the following:

                    -  Agree to practice effective barrier contraception during the entire study
                       treatment period and through 90 days after the last dose of study drug, OR

                    -  Must also adhere to the guidelines of any treatment-specific pregnancy
                       prevention program, if applicable, OR lifestyle of the subject. (Periodic
                       abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods]
                       and withdrawal are not acceptable methods of contraception.)

          -  Willing to follow the requirements of the Pomalyst Risk Evaluation and Mitigation
             Strategy (REMS) program

          -  Willing to provide bone marrow and blood samples for planned research

        Exclusion Criteria:

          -  Refractory to pomalidomide

          -  Concurrent amyloid light chain (AL) amyloidosis with organ involvement

          -  Diagnosed or treated for another malignancy =< 2 years prior to registration or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type
             are not excluded if they have undergone complete resection

          -  Any of the following because this study involves an investigational agent, whose
             genotoxic, mutagenic and teratogenic effects, on the developing fetus and newborn are
             unknown:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Other concurrent chemotherapy, or any ancillary therapy considered investigational.
             NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and
             are thus allowed while on protocol treatment

          -  Major surgery =< 14 days prior to registration

          -  Evidence of current uncontrolled cardiovascular conditions, including hypertension,
             cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial
             infarction =< 6 months. Note: Prior to entry, any electrocardiogram (ECG) abnormality
             at screening must be documented by the investigator as not medically relevant

          -  Known human immunodeficiency virus (HIV) positive

          -  Known hepatitis B surface antigen-positive status, or known or suspected active
             hepatitis C infection

          -  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 (i.e., 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) deoxyribonucleic acid (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)

          -  Any serious medical or psychiatric illness that could, in the investigator?s opinion,
             potentially interfere with the completion of treatment according to this protocol

          -  Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal
             antibodies or human proteins, or their excipients (refer to respective package inserts
             or investigator's brochure) or known sensitivity to mammalian-derived products

          -  Known chronic obstructive pulmonary disease with a forced expiratory volume in 1
             second (FEV1) < 50% of predicted normal

          -  Known moderate or severe persistent asthma within the past 2 years or currently has
             uncontrolled asthma of any classification

          -  Total bilirubin =< 1.5 x ULN (except for patients with Gilbert?s syndrome)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response rate to the therapy
Time Frame:Up to 3 years
Safety Issue:
Description:A success will be defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures

Measure:Overall survival time
Time Frame:From registration to death due to any cause, assessed up to 3 years
Safety Issue:
Description:The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measure:Progression-free survival
Time Frame:From registration to the earliest date of documentation of disease progression on initial therapy or death due to any cause, assessed up to 3 years
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Academic and Community Cancer Research United

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