Clinical Trials /

Phase II Study of Daratumumab Pre-Mobilization and Post-ASCT in Multiple Myeloma

NCT04230031

Description:

This study will use the drug daratumumab in patients who did not achieve at least a very good partial response (VGPR) and are already planned to have an Autologous Stem Cell Transplant (ASCT). Daratumumab will be given before the stem cell collection to attempt to get rid of any multiple myeloma cells that may be present in the stem cell collection and after the ASCT to get rid of any multiple myeloma cells that may be remaining.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Daratumumab Pre-Mobilization and Post-ASCT in Multiple Myeloma
  • Official Title: LCI-HEM-MYE-PurD-001: Phase II Study of Daratumumab Pre-Mobilization and Post-Autologous Stem Cell Transplant in Patients With Multiple Myeloma and Sub-Optimal Response to Induction

Clinical Trial IDs

  • ORG STUDY ID: LCI-HEM-MYE-PURD-001
  • SECONDARY ID: 00040671
  • NCT ID: NCT04230031

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
DaratumumabDarzalex1: Daratumumab

Purpose

This study will use the drug daratumumab in patients who did not achieve at least a very good partial response (VGPR) and are already planned to have an Autologous Stem Cell Transplant (ASCT). Daratumumab will be given before the stem cell collection to attempt to get rid of any multiple myeloma cells that may be present in the stem cell collection and after the ASCT to get rid of any multiple myeloma cells that may be remaining.

Detailed Description

      This is a single arm, two-stage, phase II study to evaluate the rate of â ¥ Complete Response
      (CR) post-Autologous Stem Cell Transplant (ASCT) in Multiple Myeloma (MM) subjects who failed
      to achieve at least a Very Good Partial Response (VGPR) post initial induction therapy for
      newly diagnosed disease, and for whom an ASCT is planned. Subjects will be treated with four
      weekly doses of daratumumab before mobilization for Hematopoietic Progenitor Cells (HPC)
      collection, followed by high dose chemotherapy and ASCT and four weekly doses of daratumumab
      after ASCT. A two-stage design will be implemented. Twenty three (23) subjects will be
      enrolled in the first stage, and if at least 12 of the 23 subjects have at least a CR after
      ASCT, an additional 16 subjects will be enrolled in the second stage (a total of 39
      subjects).
    

Trial Arms

NameTypeDescriptionInterventions
1: DaratumumabExperimentalPre-ASCT and Post-ASCT: Daratumumab
  • Daratumumab

Eligibility Criteria

        Inclusion Criteria

        Subject must meet all of the following applicable inclusion criteria to participate in this
        study:

          1. Written informed consent and HIPAA authorization for release of personal health
             information. NOTE: HIPAA authorization may be included in the informed consent or
             obtained separately.

          2. ≥ 18 years of age

          3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 28 days
             prior to day 1 of daratumumab.

          4. Failure to achieve a VGPR or better per IMWG 2016 criteria following a three-drug
             induction regimen for newly diagnosed MM. Subjects must have achieved at least minimal
             response to induction therapy.

          5. Measurable disease at time of diagnosis (collected within 42 days prior to initiation
             of initial induction therapy) defined as:

               1. Serum M-protein ≥ 0.5. g/dL OR

               2. Urine M-protein ≥ 200 mg/24 h OR

               3. Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is
                  abnormal

          6. ASCT is planned for post-induction therapy.

          7. Prior radiotherapy must be completed at least 14 days prior to day 1 of daratumumab
             and subject must have recovered from any radiation-induced toxicities.

          8. Recovered from all reversible acute toxic effects of induction therapy (other than
             alopecia) to ≤Grade 1 or baseline.

          9. Demonstrate adequate organ function within 28 days of day 1 of daratumumab as defined
             in the table below:

               -  White Blood Cell (WBC) ≥ 2,000/mm3

               -  Absolute Neutrophil Count (ANC) ≥ 1,000/mm3 without growth factors for 1 week
                  prior

               -  Hemoglobin (Hgb) ≥ 8 g/dL

               -  Platelet count ≥ 70,000/mm3 if bone marrow plasmacytosis of <50%; otherwise ≥
                  50,000/mm3(*)

               -  Serum creatinine OR Creatinine clearance ≤ 1.5 × upper limit of normal (ULN) OR ≥
                  30 mL/min as measured by a 24-hour urine collection or estimated by the Cockcroft
                  - Gault formula

               -  Bilirubin ≤ 2 × ULN; < 3.0 for subjects with Gilbert's Syndrome

               -  Aspartate aminotransferase (AST) ≤ 2.5× ULN

               -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN

         10. Females of childbearing potential (FCBP) must have a negative serum pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to day
             1 of daratumumab. NOTE: Females are considered of child bearing potential unless they
             are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no
             menses without an alternative medical cause).

         11. FCBP must be willing to use a highly effective contraceptive method (i.e., achieves a
             failure rate of <1% per year when used consistently and correctly) from the time of
             informed consent until 90 days (3 months) after the last dose of daratumumab.
             Contraceptive methods with low user dependency are preferable but not required.

         12. Male subjects who are sexually active with a FCBP must be willing to use condoms from
             the time of informed consent until 3 months after the last dose of daratumumab has
             been discontinued. The FCBP partner should also consider contraception recommendations
             (see inclusion #11).

         13. As determined by the enrolling physician, ability of the subject to understand and
             comply with study procedures for the entire length of the study.

        Exclusion Criteria

        Subjects meeting any of the criteria below may not participate in the study:

          1. Active infection requiring systemic therapy (i.e., involving IV antibiotics)

          2. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study, and any female subject must agree not to donate eggs
             during the study and for 3 months after the last dose of daratumumab).

          3. Has a known additional malignancy that is active and/or progressive requiring
             treatment; exceptions include basal cell or squamous cell skin cancer, in situ
             cervical or bladder cancer, carcinoma of the prostate with a current PSA value of <0.5
             ng/mL or other cancer for which the subject has completed treatment, been disease-free
             for at least five years, and is considered by Sponsor-Investigator to be at <30% risk
             of relapse, or on hormonal therapy for a history of either prostate cancer or breast
             cancer, provided that there has been no evidence of disease progression during the
             previous three years.

          4. Non-secretory MM.

          5. Active involvement of the central nervous system by MM.

          6. Prior cerebrovascular accident with persistent neurological deficit.

          7. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein, and skin changes).

          8. Had major surgery within 2 weeks prior to day 1 of daratumumab.

          9. Treatment with any investigational drug within 4 weeks prior to day 1 of daratumumab.

         10. Uncontrolled clinically significant illness including, but not limited to,
             uncontrolled hypertension (as per the most updated Joint National Committee for the
             Management of Hypertension definitions), symptomatic congestive heart failure (as per
             New York Heart Association [NYHA] class III or IV [see Appendix C], uncontrolled
             angina pectoris, myocardial infarction within the past 6 months from consent, known or
             suspected amyloidosis, uncontrolled cardiac arrhythmia, psychiatric illness/social
             situations that would limit compliance with study requirements as determined by the
             investigator, or any other condition (including laboratory abnormalities) that would,
             in the opinion of the Sponsor-Investigator, place the subject at unacceptable risk if
             he/she were to participate in the study.

         11. Known allergies, hypersensitivity or intolerance to monoclonal antibodies or human
             proteins, daratumumab or its excipients.

         12. 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.

         13. Known to be 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).

         14. Is known to be seropositive for human immunodeficiency virus.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response (CR) Rate Post-ASCT
Time Frame:up to 100 days post-ASCT
Safety Issue:
Description:CR or better will be determined for each subject as binary variables indicating whether or not best overall response post-ASCT is a CR or better as determined by the IMWG 2016 response criteria.

Secondary Outcome Measures

Measure:VGPR+ Rate
Time Frame:up to 100 days post-ASCT
Safety Issue:
Description:Post ASCT VGPR+ response will be determined for each subject as a binary variable indicating whether or not the subject achieved a post-ASCT response of VGPR or better as determined by the IMWG response criteria
Measure:Time to First Response (TTFR)
Time Frame:up to 100 days post-ASCT
Safety Issue:
Description:TTFR is defined as the time from start of induction therapy to the time when the first occurrence of a post-ASCT VGPR or better was achieved.
Measure:Time to Best Response (TTBR)
Time Frame:up to 100 days post-ASCT
Safety Issue:
Description:TTBR is defined as the time from start of induction therapy to the time when the best response of VGPR or better was achieved.
Measure:Duration of Response (DOR)
Time Frame:up to 7 years
Safety Issue:
Description:DoR will be calculated separately for each subject achieving PR or better, VGPR or better, and CR or better. The DoR intervals will be calculated from the time of the first assessment that identified response until disease progression or death from any cause.
Measure:Progression-Free Survival (PFS)
Time Frame:up to 7 years
Safety Issue:
Description:PFS is defined as the duration of time from start of induction therapy to first occurrence of either progressive disease or death from any cause
Measure:Time to Progression (TTP)
Time Frame:up to 7 years
Safety Issue:
Description:TTP will be calculated in the same fashion as described for PFS with the exception that for subjects who die for causes other than disease progression.
Measure:Time to Next Treatment (TTNT)
Time Frame:up to 7 years
Safety Issue:
Description:TTNT will be calculated from start of induction therapy until the start of the first subsequent anti-cancer therapy after all protocol directed therapy is completed.
Measure:Overall Survival (OS)
Time Frame:up to 7 years
Safety Issue:
Description:OS is defined as the duration from start of induction therapy to the date of death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Saad Z. Usmani, MD

Last Updated

January 13, 2020