Using Darzalex Faspro to lower antibody levels before stem cell transplant
A Pilot Study of 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
This study is testing if a new treatment called Darzalex Faspro can help lower harmful antibodies in adults so they can safely receive a stem cell transplant for blood cancers.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 8 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Academic / other |
| Drugs / interventions | Daratumumab, radiation |
| Locations | 1 site (Baltimore, Maryland) |
| Trial ID | NCT06398457 on ClinicalTrials.gov |
What this trial studies
This research investigates the safety and effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) in lowering donor specific antibody (DSA) levels in adult patients at high risk of primary graft failure due to elevated DSA. The study aims to enable these patients to proceed with allogeneic peripheral blood stem cell transplantation (alloBMT), which is a critical treatment for various hematologic malignancies. Participants will be monitored for their DSA levels and overall health to assess the intervention's impact on transplant eligibility and outcomes.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with high DSA levels who are eligible for reduced intensity conditioning allogeneic peripheral blood stem cell transplantation.
Not a fit: Patients with low DSA levels or those who do not meet the eligibility criteria for the transplant may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve transplant success rates for patients with high DSA levels.
How similar studies have performed: Other studies have explored desensitization methods for transplant candidates, but the specific use of Darzalex Faspro in this context is novel.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Baltimore, Maryland
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — Baltimore, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Christian B Gocke, MD, PhD — Johns Hopkins University
- Study coordinator: Christian B Gocke, MD PhD
- Email: cgocke2@jhmi.edu
- Phone: 4109558839
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.