Clinical Trials /

Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

NCT04151667

Description:

This is a Phase II study of daratumumab based therapies for older adults with multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma
  • Official Title: Phase II Study of Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: MCC-20130
  • NCT ID: NCT04151667

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Daratumumab InjectionDarzalexA: Daratumumab & Dexamethasone
Dexamethasone OralDecadronA: Daratumumab & Dexamethasone
Lenalidomide PillRevlimidB: Daratumumab, Dexamethasone and Lenalidomide
Bortezomib InjectionVelcadeC: Daratumumab, Dexamethasone and Bortezomib

Purpose

This is a Phase II study of daratumumab based therapies for older adults with multiple myeloma.

Detailed Description

      In this response adapted approach, older adults with newly diagnosed symptomatic multiple
      myeloma will receive daratumumab and dexamethasone for 2 months. Patients who achieve a
      partial response or better will continue on daratumumab. Patients who achieve less than a
      partial response will have lenalidomide or bortezomib added to their therapy. Patients who
      experience progressive disease on daratumumab after the initial 2 months of monotherapy or on
      the combination of daratumumab and either lenalidomide or bortezomib will come off study
    

Trial Arms

NameTypeDescriptionInterventions
A: Daratumumab & DexamethasoneExperimentalAll participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.
  • Daratumumab Injection
  • Dexamethasone Oral
B: Daratumumab, Dexamethasone and LenalidomideExperimentalParticipants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.
  • Daratumumab Injection
  • Dexamethasone Oral
  • Lenalidomide Pill
C: Daratumumab, Dexamethasone and BortezomibExperimentalParticipants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m^2 Days 1,8 and 15 of each 28 day treatment cycle.
  • Daratumumab Injection
  • Dexamethasone Oral
  • Bortezomib Injection

Eligibility Criteria

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form

          -  Age 65 years or older and presence of coexisting conditions which in the opinion of
             the treating physician are likely to result in the development of unacceptable side
             effects associated with high-dose chemotherapy with stem-cell transplantation

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Diagnosed with multiple myeloma and be considered to have active disease with either
             elevated Calcium, Renal Failure, Anemia, Bone Lesions (CRAB) criteria (hypercalcemia,
             renal failure, anemia, or bone lesions) or myeloma defining events (bone marrow ≥ 60%
             plasma cells, serum free light chain (sFLC) ratio≥ 100 or MRI or Positron Emission
             Tomogrphy [PET] defined lesions). Patients must not have received an active
             chemotherapy regimen. Patients may have received palliative radiotherapy at least 2
             weeks prior to the study start. Dexamethasone up to 160 mg total dose is allowed prior
             to participation

          -  Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted
             in a 24-hour urine collection sample) or by serum free light chains (involved free
             light chain greater than 100mg/L)

          -  Eastern Cooperative Group (ECOG) Performance Status of 0 or 2.

          -  Serum bilirubin levels </=1.5 times the upper limit of the normal range for the
             laboratory (ULN).

          -  Serum Aspirtate Transaminase (AST) or serum Alanine Aminotransferase (ALT) levels </=2
             x Upper Limit of Normal (ULN)

          -  Must have adequate bone marrow function: a. Absolute neutrophil count > 1,000
             cells/mm3 (1.0 x 109/L). b. Platelets >/= 75,000 /mm3.

          -  Hemoglobin > 8 g/dL (transfusions are allowed)

          -  Calculated creatinine clearance >/=30ml/min by Cockcroft-Gault formula.

          -  Men must agree to use a latex condom during sexual contact with a female of child
             bearing potential even if they have had a successful vasectomy. See Appendix C: Risks
             of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

        Exclusion Criteria:

          -  Ongoing severe infection requiring intravenous antibiotic treatment.

          -  Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in-situ cervical cancer, or other cancer from which the subject has been
             disease-free for at least 2 years.

          -  Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma
             cell dyscrasia.

          -  Patients with known Chronic Obstructive Pulmonary Disease (COPD) with a forced
             expiratory volume in 1 second (FEV1) <50% of predicted normal and , moderate or severe
             persistent asthma within the past 2 years or uncontrolled asthma. Patients with a
             history of COPD will have pulmonary function testing to include FEV1

          -  Uncontrolled medical problems such as diabetes mellitus, congestive heart failure,
             coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary,
             hepatic and renal diseases unless renal insufficiency is felt to be secondary to
             multiple myeloma.

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          -  Pregnant or lactating females.

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Concurrent use of other anti-cancer agents or treatments.

          -  Known allergy or hypersensititvity or intolerance to any of the study drugs,
             hyaluronidase, monocolonal antibodies (mAbs), human proteins, or their excipients
             (refer to daratumumab IB), or known sensitivity to mammalian derived products

          -  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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:65 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:Up to 8 months
Safety Issue:
Description:Overall Response Rate (partial response or better) of the response adapted strategy using the uniform response criteria of the International Myeloma Working Group (IMWG).

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:Progression Free Survival (PFS) from start of treatment to death of any cause, disease progression or relapse of the date of last follow-up, whichever comes first. he PFS will be estimated by the Kaplan-Meier method and 95% confidence interval (CI) will be computed by complementary log-log transformation. The 1 and 2 year PFS and 95% Confidence Intervals will be reported.
Measure:Overall Survival
Time Frame:Up to 2 years
Safety Issue:
Description:Overall Survival (OS) from start of treatment to death of any cause or the date of last follow-up, whichever comes first. OS will be estimated by the Kaplan-Meier method and 95% confidence interval will be computed by complementary log-log transformation. The 2 year OS and 95% CI will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • myeloma
  • daratumumab

Last Updated

November 4, 2019