RECRUITING

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

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 DSA donor specific antibodies desensitization BMT allogeneic stem cell transplant

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-09-19

Study Completion:2027-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06398457

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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.	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

Inclusion Criteria

Exclusion 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.
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.

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

Contacts and Locations

Study Contact

Christian B Gocke, MD PhD

CONTACT

4109558839

cgocke2@jhmi.edu

Amanda Stevens, MD

CONTACT

7869994146

msteve35@jhmi.edu

Principal Investigator

Christian B Gocke, MD, PhD

PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Study Locations (Sites)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Christian B Gocke, MD, PhD, PRINCIPAL_INVESTIGATOR, Johns Hopkins University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-19

Study Completion Date2027-03

Study Record Updates

Study Start Date2024-09-19

Study Completion Date2027-03

Terms related to this study

Keywords Provided by Researchers

DSA
donor specific antibodies
desensitization
BMT
allogeneic stem cell transplant

Additional Relevant MeSH Terms

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