Hematologic MalignancyEarly Phase 1NCT06398457
Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies
A Early Phase 1 study testing Darzalex Faspro (Daratumumab and hyaluronidase-fihj) and JH-DSA Semi-Quant Screen and Response Score in people with Hematologic Malignancy and Bone Marrow Transplant Rejection, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy, Bone Marrow Transplant Rejection, Acute Myeloid Leukemia (AML)
- What is being tested?
- Darzalex Faspro (Daratumumab and hyaluronidase-fihj) and JH-DSA Semi-Quant Screen and Response Score
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Sep 2024to Mar 2028
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Participants must be ≥18 years of age.
- Participants must have adequate organ function for undergoing RIC allogeneic peripheral blood stem cell transplant, and for undergoing a clinical trial.
- 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%.
- 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.
- Participants must have a no other readily available suitable alternative donor.
- All potential Participants must be pre-approved by BMT faculty consensus.
- Participants must have adequate willingness to participate in a clinical trial.
Who cannot join
- Previous exposure to Daratumumab-SC or other anti-CD38 therapy
- Exposure to Daratumumab-SC or other anti-CD38 therapies (unless a re-treatment study)
- 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.
- 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
- 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.
- 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.
Show all 15Show fewer
- Known hypersensitivity or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients
- Diagnosis of multiple myeloma or Amyloid light-chain (AL) amyloidosis
- A planned myeloablative alloBMT or the planned use of bone marrow or cord blood as a stem cell source
- History of HIV infection at any time in past.
- 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.
- 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)
- Clinically significant cardiac disease, including:
- 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)
- Uncontrolled cardiac arrhythmia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
Christian Gocke, MD, 443-287-7104, cgocke2@jhmi.edu
Phirun Mindel, RN, 4432870388, pvang1@jhmi.edu
About this study
Official title: A Pilot Study of Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies
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.
Read the 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.
- Conditions
- Hematologic Malignancy, Bone Marrow Transplant Rejection, Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS), Acute Lymphoblastic Leukemia (ALL), Adult, Multiple Myeloma
- Being tested
- Darzalex Faspro (Daratumumab and hyaluronidase-fihj), JH-DSA Semi-Quant Screen and Response Score
- Keywords
- DSA, donor specific antibodies, desensitization, BMT, allogeneic stem cell transplant
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Multiple Myeloma, Anemia, Aplastic, Lymphoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darzalex Faspro (Daratumumab and hyaluronidase-fihj)Drug
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.
JH-DSA Semi-Quant Screen and Response ScoreDevice
Also called JH-DSA Semi-Quant Screen Score, JH-DSA Semi-Quant Response Score
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.
| Study group | Role | What they receive |
|---|---|---|
| Daratumumab-SC followed by standard of care DSA desensitization and alloBMT | Experimental | Darzalex Faspro (Daratumumab and hyaluronidase-fihj) will be administered subcutaneously (SC) weekly (every 7 day +/- 1 day) for a total of four doses followed by standard desensitization regimen and allogeneic stem cell transplant. Receives: Drug: Darzalex Faspro (Daratumumab and hyaluronidase-fihj); Device: JH-DSA Semi-Quant Screen and Response Score |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy as assessed by percentage of patients with reduced DSA levels
Efficacy as assessed by the percentage of patients with DSA levels that are reduced to a level permissible for RIC alloHSCT with DSA strength of II or less and at least a 10% decrease in MFI from the baseline as determined by the JH-DSA Response Score.
Measured: 2 years
Safety as assessed by proportion of patients with grade 3 or higher toxicities
Proportion of patients with Grade 3 or higher toxicities attributable to daratumumab for one cycle of Darzalex Faspro
Measured: 2 years
Secondary outcomes (4)
Time (days) to neutrophilic recovery
Average amount of time taken to obtain an absolute neutrophil count (ANC) greater than or equal to 500 (10^6/L) for 3 consecutive days
Measured: 2 years
Time (days) to platelet recovery
Average amount of time taken to reach platelet count greater than 20 (10^9/L) for 3 consecutive days
Measured: 2 years
Number of participants who achieve T-cell chimerism
Number of participants who acheive T cell chimerism by day +60
Measured: 2 years
Number of participants who have primary graft failure
Number of participants who have primary graft failure defined by failure to achieve a T-cell chimerism of 5% or more or neutrophilic engraftment by day +60.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2024
- Study start19 Sep 2024
- Primary completionSep 2027 (estimated)
- Study completionMar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Daratumumab-SC (days -42, -35, -28, -21) followed by standard of care DSA desensitization and alloBMT
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- Christian B Gocke, MD, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06398457
- Sponsor's protocol ID
- J2450
- Other IDs
- IRB00440881
- Status last verified
- Sep 2026
- First submitted
- 1 May 2024
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No