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

NCT06398457 | Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: J2450IRB00440881
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

DSA; donor specific antibodies; desensitization; BMT; allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  2 years

Secondary Outcomes (4)

• Time (days) to neutrophilic recovery

  2 years

• Time (days) to platelet recovery

  2 years

• Number of participants who achieve T-cell chimerism

  2 years

• Number of participants who have primary graft failure

  2 years

Study Arms (1)

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.

Drug: Darzalex Faspro (Daratumumab and hyaluronidase-fihj); Device: JH-DSA Semi-Quant Screen and Response Score

Interventions

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.

Daratumumab-SC followed by standard of care DSA desensitization and alloBMT

JH-DSA Semi-Quant Screen and Response Score DEVICE

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.

Also known as: JH-DSA Semi-Quant Screen Score, JH-DSA Semi-Quant Response Score

Daratumumab-SC followed by standard of care DSA desensitization and alloBMT

Eligibility Criteria

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

You may qualify if:

• 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.
• 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%.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Multiple Myeloma; Anemia, Aplastic; Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Primary Myelofibrosis

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Anemia; Bone Marrow Failure Disorders; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christian B Gocke, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian B Gocke, MD PhD

CONTACT

4109558839; cgocke2@jhmi.edu

Amanda Stevens, MD

CONTACT

7869994146; msteve35@jhmi.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Daratumumab-SC (days -42, -35, -28, -21) followed by standard of care DSA desensitization and alloBMT

Study Record Dates

• First Submitted: May 1, 2024
• First Posted: May 3, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)