Trial Title:
Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies
NCT ID:
NCT06398457
Condition:
Hematologic Malignancy
Bone Marrow Transplant Rejection
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndromes (MDS)
Acute Lymphoblastic Leukemia (ALL), Adult
Multiple Myeloma
Aplastic Anemia
Lymphoma
Non Hodgkin Lymphoma
Hodgkin Lymphoma
Chronic Myeloid Leukemia
Myelofibrosis
Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Leukemia, Myeloid, Acute
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Anemia, Aplastic
Daratumumab
Conditions: Keywords:
DSA
donor specific antibodies
desensitization
BMT
allogeneic stem cell transplant
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Daratumumab-SC (days -42, -35, -28, -21) followed by standard of care DSA desensitization
and alloBMT
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Darzalex Faspro (Daratumumab and hyaluronidase-fihj)
Description:
Darzalex Faspro will be administered weekly as a subcutaneous injection on Days -42, -35,
-28 and -21 (+/- 1 day) for a total of four doses at 1800 mg each.
Arm group label:
Daratumumab-SC followed by standard of care DSA desensitization and alloBMT
Intervention type:
Device
Intervention name:
JH-DSA Semi-Quant Screen and Response Score
Description:
Serum based semi-quantifiable investigational testing regimen used to screen for high DSA
level or assess response to desensitization. It is based on results from cross-matched
flow cytometric assessment cellular-based and solid phase immunoassays (SPI) that
estimates antibody level.
Arm group label:
Daratumumab-SC followed by standard of care DSA desensitization and alloBMT
Other name:
JH-DSA Semi-Quant Screen Score
Other name:
JH-DSA Semi-Quant Response Score
Summary:
This research is being done to investigate the safety and effectiveness of Darzalex
Faspro (daratumumab and hyaluronidase-fihj) (a monoclonal antibody that targets plasma
cells that make antibodies) and whether it can lower donor specific antibodies (DSA)
levels to low enough levels to permit patients to proceed with allogeneic peripheral
blood transplant (alloBMT). Those being asked to participate have high DSA levels that
puts those being asked to participate at high risk of rejecting the available donor's
blood stem cells and making those being asked to participate ineligible to receive a stem
cell transplant.
Detailed description:
Allogeneic blood or bone marrow transplant (alloBMT) remains the definitive curative
treatment for many with relapsed or refractory hematologic malignancies. In recent years,
increased use of alternative (non-fully human leukocyte antigen (HLA)-matched) donors has
led to increased rates of donor specific antibodies (DSA). DSA are pre-formed
HLA-antibodies in the recipient directed against the donor's class I and/or class II HLA
antigens. DSA can be formed by exposure to foreign HLA antigens most commonly by
pregnancy, blood transfusions, and previous organ or blood transplantation.
High levels of circulating anti-HLA antibodies directed towards mismatched donor HLA
antigens at the time of alloBMT can dramatically increase the risk of primary graft
failure (PGF). The strength of these donor specific antibodies (DSA) can be assessed with
several methodologies including cross-matched cellular based assays (cytotoxic or flow
cytometric assessment) or the more sensitive solid phase immunoassay (SPI) that estimates
antibody level. Methods to "desensitize" patients with elevated DSAs using therapeutic
plasma exchange (TPE), intravenous immunoglobulin (IVIG), and immunosuppression (i.e.,
mycophenolate mofetil and tacrolimus) are successful in patients with moderate levels of
DSAs. However, in many patients, the DSA levels are considered too high for
desensitization, or, desensitization has failed to lower levels of the DSA, and suitable
alternative donors cannot be readily identified.
In this single-institution study at the Johns Hopkins Sidney Kimmel Comprehensive Cancer
Center (SKCCC), we will identify patients in whom alloBMT is indicated, but where DSA
levels are above a pre-defined threshold using a proprietary algorithm that combines
information from flow cytometric crossmatch (FCXM) and SPI (the Johns Hopkins (JH)-DSA
Semi-Quant Screen Score). Patients who meet eligibility criteria will undergo 4 weekly
doses of treatment with Darzalex Faspro, an anti- 38 (cluster of differentiation 38)
antibody that kills plasma cells and lowers immunoglobulin levels, followed by standard
desensitization with TPE, IVIG, and immunosuppression. Eight subjects will be treated in
this pilot study. The primary endpoint will be based on safety of Darzalex Faspro and the
number of patients who have DSA levels lowered enough to proceed to conditioning based on
a pre-defined algorithm called JH-DSA Semi-Quant Response Score.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participates must meet all other institutional criteria for the planned reduced
intensity conditioning allogeneic peripheral blood stem cell transplant (RIC
alloHSCT) as defined in Johns Hopkins BMT Policy; all potential non-cord blood donor
sources are included: matched related, haploidentical, matched unrelated, mismatched
unrelated.
2. Participants must be ≥18 years of age.
3. Participants must have adequate organ function for undergoing RIC allogeneic
peripheral blood stem cell transplant, and for undergoing a clinical trial.
a. Hematologic. i. White blood cell (WBC). ANC ≥ 500/mm3 (growth factor support
allowed). ii. Hemoglobin. No specific cut-off. (PRBC transfusion allowed). iii.
Platelets. Platelets ≥ 10,000/mm3 (platelet transfusion allowed). b. Liver.
Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and Alanine
Aminotransferase (ALT) and Aspartate Aminotransferase (AST) < 5x Upper limit of
normal (ULN) c. Renal. Serum creatinine ≤ 2.0 mg/dL. d. Cardiac. Left ventricular
ejection fraction ≥ 35%. e. Pulmonary. FEV1 ≥ 50%.
4. Subjects are eligible if there are high levels of Donor Specific Antibody levels
based on protocol specific scoring system regardless of prior attempts at standard
desensitization.
5. Participants must have a no other readily available suitable alternative donor.
6. All potential Participants must be pre-approved by BMT faculty consensus.
7. Participants must have adequate willingness to participate in a clinical trial.
Exclusion Criteria:
1. Previous exposure to Daratumumab-SC or other anti-CD38 therapy
1. Exposure to Daratumumab-SC or other anti-CD38 therapies (unless a re-treatment
study)
2. Exposure to an investigational drug (including investigational vaccine) or
invasive investigational medical device for any indication within 4 weeks or 5
pharmacokinetic half-lives, whichever is longer.
3. Focal radiation therapy within 14 days prior to beginning of planned RIC
allogeneic peripheral blood stem cell transplant regimen with the exception of
palliative radiotherapy for symptomatic management but not on measurable
extramedullary plasmacytoma
2. 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
participants suspected of having COPD and participants must be excluded if FEV1 is <
50% of predicted normal.
3. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma
of any classification. Note that participants who currently have controlled
intermittent asthma or controlled mild persistent asthma are allowed to participate.
4. Known hypersensitivity or intolerance to boron or mannitol, sorbitol,
corticosteroids, monoclonal antibodies or human proteins, or the excipients
5. Diagnosis of multiple myeloma or Amyloid light-chain (AL) amyloidosis
6. A planned myeloablative alloBMT or the planned use of bone marrow or cord blood as a
stem cell source
7. History of HIV infection at any time in past.
8. Seropositive for hepatitis B (HBV) (defined by a positive test for hepatitis B
surface antigen [HBsAg] positive, or antibodies to hepatitis B surface and/or core
antigens [antiHBs or antiHBc, respectively] with hepatitis B virus [HBV]- DNA
quantitation positive). Patients who are positive for antiHBs and/or antiHBc must
have a negative polymerase chain reaction (PCR) for HBV-DNA quantitation result
during screening. Patients with serologic findings suggestive of HBV vaccination
(antiHBs 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. Those who are PCR positive
will be excluded.
9. 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)
10. Clinically significant cardiac disease, including:
1. Myocardial infarction within 6 months before RIC alloHSCT or unstable or
uncontrolled disease/condition related to or affection cardiac function (e.g.,
unstable angina, congestive heart failure, New York Heart Association Class
III-IV)
2. Uncontrolled cardiac arrhythmia
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Address:
City:
Baltimore
Zip:
21231
Country:
United States
Status:
Recruiting
Contact:
Last name:
Christian Gocke, MD
Phone:
443-287-7104
Email:
cgocke2@jhmi.edu
Contact backup:
Last name:
Phirun Mindel, RN
Phone:
4432870388
Email:
pvang1@jhmi.edu
Start date:
September 19, 2024
Completion date:
March 2027
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Collaborator:
Agency:
Janssen Research & Development, LLC
Agency class:
Industry
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06398457
