Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide

Acute Myeloid Leukemia Clinical Trial

Official title:

Safety, Efficacy and Feasibility of Haploidentical Stem Cell Transplantation (Haplo-SCT) Using Post-Transplant Cyclophosphamide (PTCy) as an Alternative Donor Source for Patients Who Lack a Matched Sibling/Unrelated Donor Options

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03088709
• Other study ID #: 208941
• Status: Recruiting
• Phase: Phase 2
• Start date: January 18, 2017
• Est. completion date: January 31, 2022

Study information

• Verified date: April 2021
• Source: Loyola University
• Contact: Patrick A Hagen, MD
• Phone: 708-327-3156
• Email: patrick.hagen[@]lumc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Historically, the best results of allogeneic SCT have been obtained when the stem cell donor is a human leukocyte antigen (HLA)-matched sibling, however, this is only available for approximately 30 percent of patients in need for SCT. Alternative donor sources include matched unrelated donor utilizing the donor registry, cord blood transplant and mismatched donor transplant. A human leukocyte antigen (HLA)-haploidentical donor is one who shares, by common inheritance, exactly one HLA haplotype with the recipient, and includes the biologic parents, biologic children and full or half siblings. There is strong body of evidence supporting the use of haplo-SCT in patient who lack a matched sibling or unrelated donor with high rates of successful engraftment, effective Graft Versus Host Disease (GVHD) control and favorable outcomes comparative to those seen using other allograft sources, including HLA-matched sibling SCT. Furthermore, it provides a cost-efficient donor option in a timely manner especially for patients who need to proceed quickly to transplant due to concern of disease relapse/progression.

Description:

An open label, single-arm, single-center study to evaluate the safety, efficacy and feasibility of haplo-SCT as an alternative donor source for patients who lack a matched sibling/unrelated donor options. The choice of the chemotherapy treatment for transplantation will be up to the investigator. Post-transplant cyclophosphamide will serve as the backbone of the immunosuppression treatment to prevent GVHD. GVHD Prevention Treatment: Cyclophosphamide will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus will be administered IV until patient can take it by mouth starting on day of transplant and continue approximately 100 days post-transplant. Mycophenolate mofetil will be administered IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 90 Years

Eligibility

Inclusion Criteria:

• Ages 16 years old and up
• Performance Status 70 percent or above
• Patients should have the following diseases:
• Acute myelogenous leukemia (AML)
• Acute lymphocytic leukemia or lymphoblastic lymphoma (ALL)
• Transfusion dependent myelodysplastic syndrome (MDS)
• Non-Hodgkin's Lymphoma (NHL)
• Chronic lymphocytic leukemia (CLL)
• Pulmonary function as measured by forced expiratory volume at one second (FEV1) and/or corrected diffusing capacity of lung for carbon monoxide (DLCO) at 60 percent of predicted or above
• Left ventricular ejection fraction at 45 percent or above
• If the donor-specific HLA antibodies (DSA) are positive, the patient must undergo a desensitization protocol resulting in undetectable DSA prior to day of transplant

Exclusion Criteria:

• Less than twenty-one days have elapsed since the subject's last radiation or chemotherapy prior to conditioning (except for hydroxyurea)
• Uncontrolled bacterial, fungal or viral infections at time of study enrollment
• Positive for HIV, human T-cell leukemia virus (HTLV-1) and/or Hepatitis C
• Subjects with signs/symptoms of active central nervous system (CNS) disease

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Acute Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• Cyclophosphamide
IV medication given for prevention of graft versus host disease.
• Tacrolimus
IV medication given for prevention of graft versus host disease.
• Mycophenolate mofetil
IV medication given for prevention of graft versus host disease.

Other:
• Haploidentical Stem Cell Transplantation
A stem cell transplant that involves matching a patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type, with that of a related donor.

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Loyola University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chimerism	Blood test that measures amount of donor's cells	100 days
Secondary	Neutrophil engraftment	Blood test that measures the white cell count	Day 28
Secondary	Platelet engraftment	Blood test that measures the platelet count	Day 60
Secondary	Grade 3 to 4 acute graft-verus-host disease (GVHD)	National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form	100 days
Secondary	Frequency and severity of chronic GVHD	National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form	1 year
Secondary	Disease status with blast counts (immature blood cell count) above 5%	Blood work and/or bone marrow biopsy will be used	3 years
Secondary	Survival status by patient contact	Contact with patient by phone or doctor's visit	3 years
Secondary	Immune reconstitution	Blood work will be used to evaluate recovery of T and B cell count subset that assess cells which make antibodies to fight infections	3 years
Secondary	Grade 3 through 5 Adverse Events	Toxicities that are possibly, probably, and definitely related to study treatment according to NCI CTCAE Version 4	2 years