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Phase II Trial of CD24Fc for the Prevention of Acute GVHD Following Myeloablative Allogeneic HSCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02663622
Recruitment Status : Active, not recruiting
First Posted : January 26, 2016
Last Update Posted : July 24, 2020
Sponsor:
Collaborators:
Ohio State University
University of Michigan Rogel Cancer Center
Indiana University School of Medicine
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OncoImmune, Inc.

Brief Summary:
This is a multicenter prospective phase IIa dose escalation and Phase II expansion cohort clinical trial designed to determine the efficacy of CD24Fc for acute GVHD prophylaxis.

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Hematopoietic Stem Cell Transplantation Leukemia Drug: CD24Fc Drug: Methotrexate Drug: Tacrolimus Drug: Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Part 1 is double blind, placebo controlled study. Part 2 is open label.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIa and Phase II Expansion Trial of CD24Fc for Prevention of Acute Graft-versus-Host Disease Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplant
Actual Study Start Date : September 20, 2016
Actual Primary Completion Date : June 4, 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Active Comparator: CD24Fc

CD24Fc will be given in three dose cohorts. CD24Fc in 240 mg as intravenous (IV) infusion at Day -1 CD24Fc in 480 mg as intravenous (IV) infusion at Day -1 CD24Fc (480 mg (day -1), 240 mg (day +14) and 240 mg (day +28)) as intravenous infusion.

All cohorts + Tacrolimus (begin on day -3. IV [0.03mg/kg/day] or PO [0.045mg/kg/dose] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/m2/dose once daily on Day 1 after HCT, and at a dose of 10 mg/m2/dose on days 3, 6, and 11 after HCT).

Drug: CD24Fc
Acute GVHD prophylaxis
Other Name: CD24 Fusion Protein

Drug: Methotrexate
Acute GVHD prophylaxis
Other Name: Trexall

Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
  • FK506
  • Prograf

Placebo Comparator: Placebo
Placebo (saline IV injection solution) + Tacrolimus (begin on day -3. IV [0.03mg/kg/day] or PO [0.045mg/kg/dose] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/m2/dose once daily on Day 1 after HCT, and at a dose of 10 mg/m2/dose on days 3, 6, and 11 after HCT)
Drug: Methotrexate
Acute GVHD prophylaxis
Other Name: Trexall

Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
  • FK506
  • Prograf

Drug: Placebo
100 ml saline IV infusion.
Other Name: Saline Solution

Active Comparator: CD24Fc Expansion
CD24Fc (480 mg (day -1), 240 mg (day +14) and 240 mg (day +28)) + Tacrolimus (begin on day -3. IV [0.03mg/kg/day] or PO [0.045mg/kg/dose] dosing is permitted) + Methotrexate (given intravenously at a dose of 15 mg/m2/dose once daily on Day 1 after HCT, and at a dose of 10 mg/m2/dose on days 3, 6, and 11 after HCT)
Drug: CD24Fc
Acute GVHD prophylaxis
Other Name: CD24 Fusion Protein

Drug: Methotrexate
Acute GVHD prophylaxis
Other Name: Trexall

Drug: Tacrolimus
Acute GVHD prophylaxis
Other Names:
  • FK506
  • Prograf




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


Secondary Outcome Measures :
  1. One year overall survival (OS) [ Time Frame: One year ]
    This is to assess the one year overall survival.

  2. One year disease free survival (DFS) [ Time Frame: One year ]
    This is to assess the one year disease (relapse) free survival.

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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


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): NCT02663622


Locations
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United States, Indiana
Indiana University School of Medicine
Indianapolis, Indiana, United States, 46202
United States, Michigan
The University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
OncoImmune, Inc.
Ohio State University
University of Michigan Rogel Cancer Center
Indiana University School of Medicine
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Pavan Reddy, MD University of Michigan Rogel Cancer Center
Publications:
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Responsible Party: OncoImmune, Inc.
ClinicalTrials.gov Identifier: NCT02663622    
Other Study ID Numbers: UMCC 2015.181
HUM00107805 ( Other Identifier: University of Michigan )
15-4789 ( Other Identifier: Orphan Drug Designation )
R44CA221513 ( U.S. NIH Grant/Contract )
R44CA246991 ( U.S. NIH Grant/Contract )
First Posted: January 26, 2016    Key Record Dates
Last Update Posted: July 24, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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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Graft vs Host Disease
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
Calcineurin Inhibitors