Phase II Trial of CD24Fc for the Prevention of Acute GVHD Following Myeloablative Allogeneic HSCT
- Inclusion Criteria 4.1.1 A prospective patient for allogeneic HCT for a malignant hematologic disorder (see section 4.1.3 for eligible diagnoses). 4.1.2 The donor and recipient must have an 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. 4.1.3 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. Chronic Myelogenous Leukemia (CML) in first or subsequent chronic phase failing to respond (or intolerant) to at least two different tyrosine kinase inhibitors. CML in accelerated or blast phase (CML-AP/BP) are eligible without requirement to fail tyrosine kinase inhibitor therapy, but must be in remission at time of enrollment. 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. 3. Myelodysplastic syndrome (MDS) with intermediate or high-risk IPSS or equivalent IPSS-R score with < 10% blasts in the bone marrow. 4. Chronic Myelomonocytic Leukemia (CMML) with < 10% blasts in the bone marrow. 4.1.4 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. 4.1.5 Karnofsky Performance Status >70%, see Appendix A. 4.1.6 Patients must have normal or near normal organ function as defined by their treating institutions BMT program clinical practice guidelines. In addition, for purposes of this protocol minimum organ function criteria within 21 days of beginning conditioning include: TABLE 1: Eligibility According to Pre HCT Organ Function Total bilirubin ≤2.5 mg% (unless from Gilbert's disease or disease-related) AST(SGOT)/ALT(SGPT) <5.0 X institutional upper limit of normal Estimated or actual GFR >50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (GFR should be corrected for BSA) Pulmonary Function Tests* DLCO, FEV1, FVC > 50% DLCO should be corrected for hemoglobin Ejection Fraction* >50% Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) ≤ 5 *May be assessed up to 6 weeks prior to the start of conditioning therapy 4.1.7 Ability to understand and the willingness to sign a written informed consent document. 4.1.8 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 (See section 6.0). Exclusion Criteria: 4.2.1 Subjects may not have presence of active CNS disease or extramedullary disease. 4.2.2 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). 4.2.3 Cord blood and haploidentical donors are not eligible. 4.2.4 HLA-mismatch at the HLA-A, -B, -C, and - DRB1 loci. Note, HLA-DQ mismatches are permissible. 4.2.5 Pregnant and nursing mothers are excluded from this study. This is because the risk to the fetus is unknown. 4.2.6 Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient or raise concern that the patient would not comply with protocol procedures. 4.2.7 Uncontrolled infections. Patients 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. 4.2.8 Patients seropositive or PCR positive for the human immunodeficiency virus (HIV). Patients with evidence of Hepatitis B or Hepatitis C PCR positivity. 4.2.9 Prior HCT (allograft or prior autograft). 4.2.10 Use of T cell depletion either ex vivo or in vivo (i.e. ATG, alemtuzumab) is prohibited. 4.2.11 Current or prior diagnosis of antecedent Myelofibrosis is excluded.
The first part of study is a Phase IIa randomized, double blind, placebo controlled, multi-center study to investigate adding CD24Fc to standard of care tacrolimus and methotrexate in acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT) with matched unrelated donors in treatment of leukemia and myelodysplastic syndrome. Three dose cohorts are planned with 240 mg at day -1, 480 mg at day -1, and the multi-dose cohort of 480-240-240 mg at day -1, day 14 and day 28. The CD24Fc : placebo ratio is 3:1. The second part is a prospective phase II expansion cohort trial investigating the addition of CD24Fc to standard acute graft-versus host disease (GVHD) prophylaxis for allogeneic hematopoietic stem cell transplantation (HCT). Based on the Phase IIa safety results and the pharmacokinetic data, the Phase II expansion dose will be the multi-dose 480-240-240 mg regimen administered on day -1, day 14 and day 28. The primary objective of phase II expansion is to determine if the addition of CD24Fc to standard GVHD prophylaxis improves 180 days grade III-IV acute GVHD-free survival (AGFS) when compared to CIBMTR database registered control patients who had standard GVHD prophylaxis alone. Eligible patients will be those requiring allogeneic HCT for malignant hematologic conditions and receiving a myeloablative conditioning regimen. An unrelated donor is required to match at HLA-A, -B, -C, and -DRB1 loci.
Trial Phase Phase II
Trial Type Treatment
- Primary ID UMCC 2015.181
- Secondary IDs NCI-2017-00017, R44CA246991, HUM00107805, R44CA221513, FD-R-6089, 15-4789, R01FD006089
- Clinicaltrials.gov ID NCT02663622