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CD24Fc for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005) (CATHY)

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ClinicalTrials.gov Identifier: NCT04095858
Recruitment Status : Active, not recruiting
First Posted : September 19, 2019
Last Update Posted : August 5, 2021
Sponsor:
Information provided by (Responsible Party):
OncoImmune, Inc.

Brief Summary:
The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens: CD24Fc vs placebo with the standard GVHD prophylaxis of tacrolimus / methotrexate.

Condition or disease Intervention/treatment Phase
Hematopoietic Stem Cell Transplantation Acute Graft Versus Host Disease Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Drug: CD24Fc Drug: Placebo Drug: Methotrexate Drug: Tacrolimus Phase 3

Detailed Description:
The study compares two acute graft-versus-host disease (aGVHD) prophylaxis regimens: CD24Fc/tacrolimus / methotrexate (CD24Fc/Tac/MTX) versus placebo/tacrolimus / methotrexate (placebo/Tac/MTX) in the setting of myeloablative conditioning (MAC), matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation in participants with acute leukemia (AML/ALL) or myelodysplastic syndrome (MDS). The study agent, CD24Fc, will be administered through IV infusion on days -1, 14, and 28 at the dose of 480mg, 240 mg and 240mg, respectively. The placebo will be 100 ml normal saline intravenous (IV) solution.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Placebo Controlled, Multi-center, Phase III Study of CD24Fc for Prevention of Acute Graft-versus-host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : January 5, 2021
Estimated Primary Completion Date : November 2, 2021
Estimated Study Completion Date : November 2, 2021


Arm Intervention/treatment
Experimental: CD24Fc Treatment
CD24Fc: IV infusion, 480 mg (day -1), 240 mg (day +14) and 240 mg (day +28); Tacrolimus: begin on day -3. IV [0.03 mg/kg/day] or by mouth (PO) [0.045 mg/kg/dose] dosing is permitted; Methotrexate: given IV at a dose of 15 mg/m^2/dose once daily on Day 1 after hematopoietic cell transplantation (HCT), and at a dose of 10 mg/m^2/dose on days 3, 6, and 11 after HCT.
Drug: CD24Fc
IV infusion: 480 mg at Day -1, 240 mg at Day 14, 240 mg at Day 28.
Other Name: Human CD24 and human IgG Fc Fusion Protein

Drug: Methotrexate
IV, 15 mg/m^2/dose at Day 1, then 10 mg/m2/dose at Day 3, 6, 11.
Other Name: Trexall

Drug: Tacrolimus
Begin on day -3. IV [0.03 mg/kg/day] or PO [0.045 mg/kg/dose] dosing is permitted
Other Names:
  • FK506
  • Prograf

Placebo Comparator: Placebo
Placebo (Saline solution): 100 ml IV infusion, Day -1, Day 14, Day 28. Tacrolimus: begin on day -3. IV [0.03mg/kg/day] or PO [0.045 mg/kg/dose] dosing is permitted; Methotrexate: given IV at a dose of 15 mg/m^2/dose once daily on Day 1 after HCT, and at a dose of 10 mg/m^2/dose on days 3, 6, and 11 after HCT.
Drug: Placebo
IV infusion, 100 ml at Day -1, Day 14, and Day 28.
Other Name: Saline

Drug: Methotrexate
IV, 15 mg/m^2/dose at Day 1, then 10 mg/m2/dose at Day 3, 6, 11.
Other Name: Trexall

Drug: Tacrolimus
Begin on day -3. IV [0.03 mg/kg/day] or PO [0.045 mg/kg/dose] dosing is permitted
Other Names:
  • FK506
  • Prograf




Primary Outcome Measures :
  1. 180 day grade III-IV acute GVHD free survival (AGFS) [ Time Frame: Up to 180 days after HCT ]
    180 day grade III-IV acute GVHD free survival (AGFS) is a composite endpoint to determine the Grade III-IV AGFS in 180 days after HCT. The onset day of Grade III-IV aGVHD, or death of any cause, which comes the first, will be counted as the event.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 180 days ]
    OS is defined as the time of all-cause mortality after HCT.

  2. Disease Free Survival (DFS) [ Time Frame: Up to 180 days ]
    DFS is defined as the earlier of time of leukemia relapse, or death, whichever occurs first.

  3. 180 day grade II-IV acute GVHD free survival (AGFS) [ Time Frame: Up to 180 days ]
    180 day grade II-IV acute GVHD free survival (AGFS) is a composite endpoint to determine the Grade II-IV AGFS 180 days after HCT. The onset day of Grade II-IV aGVHD, or death of any cause, whichever comes the first, will be counted as the event.

  4. 180 day grade III-IV acute GVHD relapse-free survival (AGRFS) [ Time Frame: Up to 180 days ]
    180 day grade III-IV acute GVHD relapse-free survival (AGRFS) is a composite endpoint to determine the Grade III-IV AGRFS 180 days after HCT. The onset day of Grade III-IV aGRFS, relapse, or death of any cause, whichever comes first, will be counted as the event.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A prospective participant for allogeneic HCT for a malignant hematologic disorder.
  2. The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and - DRB1 loci. High-resolution typing is required for all alleles for unmatched donors. Only matched unrelated donors are acceptable for this trial.
  3. The following diagnoses are to be included:

    1. Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or second remission. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, < 5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
    2. Myelodysplastic syndrome (MDS) with intermediate or high-risk International Prognostic Scoring System (IPSS) or equivalent Revised International Prognostic Scoring System (IPSS-R) score with < 10% blasts in the bone marrow.
  4. Males or non-pregnant, non-lactating females, ≥ 18 years of age. Note there is no defined upper age limited, so long as deemed appropriate candidate for myeloablative conditioning.
  5. Karnofsky Performance Status >70%.
  6. Participants must have normal or near normal organ function as defined by their treating institutions bone marrow transplant (BMT) program clinical practice guidelines. In addition, for purposes of this protocol minimum organ function criteria within 30 days of beginning conditioning include: Eligibility According to Pre HCT Organ Function:

    1. Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related);
    2. Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT))/ alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT)) <5.0 X institutional upper limit of normal;
    3. Estimated or actual glomerular filtration rate (GFR)>50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal (GFR should be corrected for BSA);
    4. Pulmonary Function Tests include diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), forced vital capacity (FVC)> 50% DLCO should be corrected for hemoglobin;
    5. Ejection Fraction >50%;
    6. Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5.

    Item d and e may be assessed up to 10 weeks prior to the start of conditioning therapy.

  7. Ability to understand and the willingness to sign a written informed consent document.
  8. Women of child bearing potential and men must agree to use contraception prior to study entry and through day 100 post HCT (hormonal or barrier method of birth control; abstinence). Should a woman become pregnant or suspect she is pregnant while she or her partner is on treatment in this study, she should inform her study physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study until day 100 post HCT.

Exclusion Criteria:

  1. Subjects may not have presence of active central nervous system (CNS) disease or extramedullary disease.
  2. Prior cytotoxic chemotherapy within 21 days from the initiation of HCT conditioning (i.e. intensive induction / consolidation for AML). Note, certain low intensity treatments not intended to induce remission but rather stabilize disease are acceptable up to 24 hrs prior to initiation of HCT conditioning (i.e. Tyrosine Kinase Inhibitor, sorafenib).
  3. Cord blood and haploidentical donors are not eligible.
  4. HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are permissible.
  5. Pregnant and nursing mothers are excluded from this study. This is because the risk to the fetus is unknown.
  6. Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the participant or raise concern that the participant would not comply with protocol procedures.
  7. Uncontrolled infections. Participants still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiologic, clinical and/or culture) that the infection is well controlled.
  8. Participants seropositive or polymerase chain reaction (PCR) positive for the human immunodeficiency virus (HIV). Participants with evidence of Hepatitis B or Hepatitis C PCR positivity.
  9. Prior HCT (allograft or prior autograft).
  10. Use of T cell depletion either ex vivo or in vivo (i.e. anti-thymocyte globulin (ATG), alemtuzumab) is prohibited.
  11. Current or prior diagnosis of antecedent Myelofibrosis is excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04095858


Locations
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United States, California
City of Hope ( Site 0302)
Duarte, California, United States, 91010
United States, Illinois
The University of Chicago Medical Center ( Site 0306)
Chicago, Illinois, United States, 60637
United States, Pennsylvania
Penn State University Milton S. Hershey Medical Center ( Site 0304)
Hershey, Pennsylvania, United States, 17033
Abramson Cancer Center of the University of Pennsylvania ( Site 0309)
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
OncoImmune, Inc.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: OncoImmune, Inc.
ClinicalTrials.gov Identifier: NCT04095858    
Obsolete Identifiers: NCT04976699
Other Study ID Numbers: 7110-005
15-4789 ( Other Identifier: FDA Orphan Drug Designation )
FD-OOPD-006089 ( Other Grant/Funding Number: FDA Orphan Products Clinical Trial Grant )
CD24Fc-005-CATHY ( Other Identifier: OncoImmune )
MK-7110-005 ( Other Identifier: Merck Protocol Number )
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: August 5, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Graft vs Host Disease
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors