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Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide

Phase 2
Terminated
Conditions
Acute Lymphocytic Leukemia
Non-hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Interventions
Other: Haploidentical Stem Cell Transplantation
Registration Number
NCT03088709
Lead Sponsor
Loyola University
Brief 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.

Detailed 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 & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
5
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
All patients will receive HaploidenticalMycophenolate mofetilThe 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. All patients will receive a Haplo-identical stem cell transplantation. GVHD Prevention Treatment: Cyclophosphamide 50mg/kg will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus 0.03 mg/kg daily 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 15mg/kg will be administered twice a day IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.
All patients will receive HaploidenticalHaploidentical Stem Cell TransplantationThe 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. All patients will receive a Haplo-identical stem cell transplantation. GVHD Prevention Treatment: Cyclophosphamide 50mg/kg will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus 0.03 mg/kg daily 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 15mg/kg will be administered twice a day IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.
All patients will receive HaploidenticalTacrolimusThe 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. All patients will receive a Haplo-identical stem cell transplantation. GVHD Prevention Treatment: Cyclophosphamide 50mg/kg will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus 0.03 mg/kg daily 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 15mg/kg will be administered twice a day IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.
All patients will receive HaploidenticalCyclophosphamideThe 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. All patients will receive a Haplo-identical stem cell transplantation. GVHD Prevention Treatment: Cyclophosphamide 50mg/kg will be administered IV on Day 3 and Day 5 post transplant. Tacrolimus 0.03 mg/kg daily 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 15mg/kg will be administered twice a day IV until patient can take it by mouth starting on Day 1 post transplant until 28 days.
Primary Outcome Measures
NameTimeMethod
Chimerism100 days

Blood test that measures amount of donor's cells

Secondary Outcome Measures
NameTimeMethod
Grade 3 to 4 acute graft-verus-host disease (GVHD)100 days

National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form

Disease status with blast counts (immature blood cell count) above 5%3 years

Blood work and/or bone marrow biopsy will be used

Neutrophil engraftmentDay 28

Blood test that measures the white cell count

Platelet engraftmentDay 60

Blood test that measures the platelet count

Frequency and severity of chronic GVHD1 year

National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form

Survival status by patient contact3 years

Contact with patient by phone or doctor's visit

Immune reconstitution3 years

Blood work will be used to evaluate recovery of T and B cell count subset that assess cells which make antibodies to fight infections

Grade 3 through 5 Adverse Events2 years

Toxicities that are possibly, probably, and definitely related to study treatment according to NCI CTCAE Version 4

Trial Locations

Locations (1)

Loyola University Medical Center

🇺🇸

Maywood, Illinois, United States

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