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Study of Daratumumab for Decreasing Circulating Antibodies in Sensitized Patients Awaiting Heart Transplantation

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ClinicalTrials.gov Identifier: NCT04088903
Recruitment Status : Withdrawn (Protocol changed to use subcutaneous rather than intravenous daratumumab.)
First Posted : September 13, 2019
Last Update Posted : October 28, 2020
Sponsor:
Information provided by (Responsible Party):
Ronald Witteles, Stanford University

Brief Summary:
The purpose of this study is to test whether daratumumab, a drug that eliminates antibody-producing plasma cells, can effectively lower the level of preformed antibodies in patients awaiting heart transplantation. These preformed antibodies limit the number of donor hearts that are compatible for the patients. If daratumumab can effectively remove preformed, donor-specific antibodies, then highly allosensitized patients will have more compatible hearts available to them, potentially decreasing transplant waitlist time and reducing mortality.

Condition or disease Intervention/treatment Phase
Allosensitization Heart Transplant Failure and Rejection Drug: Daratumumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Daratumumab for Reduction of Circulating Antibodies in Patients With High Allosensitization Awaiting Heart Transplantation
Estimated Study Start Date : April 1, 2021
Estimated Primary Completion Date : April 1, 2023
Estimated Study Completion Date : April 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Daratumumab infusion
  • Participants will receive an intravenous infusion of daratumumab weekly for 8 doses and then every other week for 2 doses.
  • For this dose-escalation study, the initial patients will receive a 2 mg/kg dose of daratumumab. In subsequent patients, the dose will be uptitrated to 16 mg/kg as tolerated.
  • Participants will undergo laboratory testing, including for circulating antibodies, at baseline, prior to each infusion session, and at the end of the study.
Drug: Daratumumab
>Daratumumab 16 mg/kg intravenous weekly for 8 weeks and then every other week for 2 doses.




Primary Outcome Measures :
  1. Change in the number of individual preformed HLA antibodies before and after daratumumab treatment. [ Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier). ]
    Will compare the number of individual circulating preformed human leukocyte antigen (HLA) antibodies (i.e., those HLA antibodies that have a mean fluorescence intensity [MFI] >3000) at baseline with the number of preformed antibodies after daratumumab treatment.


Secondary Outcome Measures :
  1. Percent MFI change for each individual preformed HLA antibody after 4 weeks of daratumumab treatment. [ Time Frame: Baseline and Week 4 (or the last measurement prior to heart transplantation, whichever is earlier). ]
    Percent change in the MFI of each circulating preformed HLA antibody from baseline to 4 weeks or the time of heart transplantation (whichever is earlier).

  2. Percent MFI change for each individual preformed HLA antibody at 8 weeks of daratumumab treatment. [ Time Frame: Baseline and Week 8 (or the last measurement prior to heart transplantation, whichever is earlier). ]
    Percent change in the MFI of each circulating preformed HLA antibody from baseline to 8 weeks or the time of heart transplantation (whichever is earlier).

  3. Change in the number of individual preformed HLA antibodies after 6 weeks of daratumumab. [ Time Frame: Baseline and Week 6 (or the last measurement prior to heart transplantation, whichever is earlier). ]
    Will compare the number of individual circulating preformed HLA antibodies at baseline with the number of preformed antibodies after 6 weeks of daratumumab treatment.

  4. Change in the percentage of calculated panel of reactive antibodies before and after daratumumab treatment. [ Time Frame: Baseline and Week 12 (or the last measurement prior to heart transplantation, whichever is earlier). ]
    Will compare the serum panel of reactive antibodies (PRA) percentage at baseline with the PRA percentage after 12 weeks of treatment with daratumumab.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant is on an active list for a heart transplant.
  • Participant has a high level of allosensitization, defined as a calculated PRA (panel of reactive antibodies) of 50%, based on their antibody status at the time of entry into the study.
  • Ability to understand and willingness to sign an informed consent form prior to any study-related procedures.
  • Women of childbearing potential must have a negative pregnancy test at screening.
  • Both male and female patients must use effective methods of birth control, must not donate eggs or sperm during the course of the study and for 3 months after stopping daratumumab.

Exclusion Criteria:

  • History of allergy or intolerance to daratumumab.
  • Prior diagnosis of myeloma or light chain amyloidosis.
  • Active infection.
  • Women who are pregnant or breastfeeding.
  • Ongoing desensitization treatment with another agent. Subjects are excluded if they have received:

    • a. IVIG within 30 days of enrollment.
    • b. Proteasome inhibitor within 60 days of enrollment.
    • c. Rituximab within 180 days of enrollment.
  • Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study.
  • Contraindication to herpes zoster prophylaxis.
  • Known to be seropositive for human immunodeficiency virus (HIV).
  • Known to be 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).
  • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal.
  • Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04088903


Sponsors and Collaborators
Ronald Witteles
Investigators
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Principal Investigator: Ronald M Witteles, MD Stanford University
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Responsible Party: Ronald Witteles, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT04088903    
Other Study ID Numbers: IRB-53476
First Posted: September 13, 2019    Key Record Dates
Last Update Posted: October 28, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ronald Witteles, Stanford University:
Immunotherapy, anti-CD38 antibody
Additional relevant MeSH terms:
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Daratumumab
Antineoplastic Agents