Clinical trial NCT03088709: Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Non-hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Keywords: NHL
Non-Hodgkin Lymphoma
Haploidentical
Bone Marrow Transplant
Stem Cell Transplant
Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Chronic Lymphocytic Leukemia
GVHD
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2017-03-23
Enrollment: 5
Sex: ALL
Minimum age (years): 16
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Chimerism
timeFrame: 100 days
Secondary outcomes:
measure: Neutrophil engraftment
timeFrame: Day 28
measure: Platelet engraftment
timeFrame: Day 60
measure: Grade 3 to 4 acute graft-verus-host disease (GVHD)
timeFrame: 100 days
measure: Frequency and severity of chronic GVHD
timeFrame: 1 year
measure: Disease status with blast counts (immature blood cell count) above 5%
timeFrame: 3 years
measure: Survival status by patient contact
timeFrame: 3 years
measure: Immune reconstitution
timeFrame: 3 years
measure: Grade 3 through 5 Adverse Events
timeFrame: 2 years
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: Cardinal Bernardin Cancer Center, Loyola University
name: Zeina Al-Mansour, MD
role: PRINCIPAL_INVESTIGATOR
References: