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

NCT04230031 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: LCI-HEM-MYE-PURD-00100040671
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate Post-ASCT

  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.

  up to 100 days post-ASCT

Secondary Outcomes (8)

• VGPR+ Rate

  up to 100 days post-ASCT

• Time to First Response (TTFR)

  up to 100 days post-ASCT

• Time to Best Response (TTBR)

  up to 100 days post-ASCT

• Duration of Response (DOR)

  up to 7 years

• Progression-Free Survival (PFS)

  up to 7 years

Study Arms (1)

1: Daratumumab

EXPERIMENTAL

Pre-ASCT and Post-ASCT: Daratumumab

Drug: Daratumumab

Interventions

Daratumumab DRUG

Experimental

Also known as: Darzalex

1: Daratumumab

Eligibility Criteria

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

You may qualify if:

• 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.
• ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 28 days prior to day 1 of daratumumab.
• 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.
• Measurable disease at time of diagnosis (collected within 42 days prior to initiation of initial induction therapy) defined as:
• Serum M-protein ≥ 0.5. g/dL OR
• Urine M-protein ≥ 200 mg/24 h OR
• Involved free light chain (FLC) level ≥ 10 mg/dL provided serum FLC ratio is abnormal
• ASCT is planned for post-induction therapy.
• 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.
• Recovered from all reversible acute toxic effects of induction therapy (other than alopecia) to ≤Grade 1 or baseline.
• 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

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Active infection requiring systemic therapy (i.e., involving IV antibiotics)
• 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).
• 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.
• Non-secretory MM.
• Active involvement of the central nervous system by MM.
• Prior cerebrovascular accident with persistent neurological deficit.
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Had major surgery within 2 weeks prior to day 1 of daratumumab.
• Treatment with any investigational drug within 4 weeks prior to day 1 of daratumumab.
• 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.
• Known allergies, hypersensitivity or intolerance to monoclonal antibodies or human proteins, daratumumab or its excipients.
• 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.
• 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).
• Is known to be seropositive for human immunodeficiency virus.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab

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

Study Officials

• Shebli Atrash, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 18, 2020
• Study Start: July 2, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 21, 2022

Record last verified: 2022-03

Locations

US (1)