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

Acute Myeloid Leukemia Clinical Trial

— CATHY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04976699
• Other study ID #: 7110-005
• Secondary ID: 15-4789FD-OOPD-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 5, 2021
• Est. completion date: November 2, 2021

Study information

• Verified date: July 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: November 2, 2021
• Est. primary completion date: November 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Graft vs Host Disease
• Hematopoietic Stem Cell Transplantation
• Leukemia
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• CD24Fc
IV infusion: 480 mg at Day -1, 240 mg at Day 14, 240 mg at Day 28.
• Placebo
IV infusion, 100 ml at Day -1, Day 14, and Day 28.
• Methotrexate
IV, 15 mg/m^2/dose at Day 1, then 10 mg/m2/dose at Day 3, 6, 11.
• Tacrolimus
Begin on day -3. IV [0.03 mg/kg/day] or PO [0.045 mg/kg/dose] dosing is permitted

Locations

Country	Name	City	State
United States	The University of Chicago Medical Center ( Site 0306)	Chicago	Illinois
United States	City of Hope ( Site 0302)	Duarte	California
United States	Penn State University Milton S. Hershey Medical Center ( Site 0304)	Hershey	Pennsylvania
United States	Abramson Cancer Center of the University of Pennsylvania ( Site 0309)	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	180 day grade III-IV acute GVHD free survival (AGFS)	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.	Up to 180 days after HCT
Secondary	Overall Survival (OS)	OS is defined as the time of all-cause mortality after HCT.	Up to 180 days
Secondary	Disease Free Survival (DFS)	DFS is defined as the earlier of time of leukemia relapse, or death, whichever occurs first.	Up to 180 days
Secondary	180 day grade II-IV acute GVHD free survival (AGFS)	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.	Up to 180 days
Secondary	180 day grade III-IV acute GVHD relapse-free survival (AGRFS)	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.	Up to 180 days