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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

ConditionsHematologic MalignancyBone Marrow Transplant RejectionAcute Myeloid Leukemia (AML)Myelodysplastic Syndromes (MDS)Acute Lymphoblastic Leukemia (ALL), AdultMultiple MyelomaAplastic AnemiaLymphomaNon Hodgkin LymphomaHodgkin LymphomaChronic Myeloid LeukemiaMyelofibrosis
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • 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 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.

Treatment groups

8 Participants
are divided into 1 treatment group
Group A: Daratumumab-SC followed by standard of care DSA desensitization and alloBMTExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
2 years
2

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

Time frame
2 years

Secondary outcomes

1

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

Time frame
2 years
2

Time (days) to platelet recovery

Average amount of time taken to reach platelet count greater than 20 (10\^9/L) for 3 consecutive days

Time frame
2 years
3

Number of participants who achieve T-cell chimerism

Number of participants who acheive T cell chimerism by day +60

Time frame
2 years
4

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.

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead sponsor

Janssen Research & Development, LLC

Collaborator

Source ClinicalTrials.gov
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