Clinical trial NCT03016806: Umbilical Cord Blood Transplantation From Unrelated Donors
Official title: Umbilical Cord Blood Transplantation From Unrelated Donors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Leukemia
Immune Deficiency Disorder
Congenital Hematological Disorder
Metabolism Disorder
Aplastic Anemia
Myelodysplastic Syndromes
Chronic Leukemia
Lymphoma
Multiple Myeloma
Solid Tumor
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2017-01-11
Enrollment: 30
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a single-center, treatment protocol with 4 possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution.

Detailed description: This study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. Enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. Patients will then receive cord blood stem cells followed by GvHD prophylaxis that will include Tacrolimus and Mycophenolate Mofetil, or Cyclosporin A and Methylprednisolone. Multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Eligibility criteria: Inclusion Criteria:

* Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to:
* Congenital and Other Non-malignant Disorders:
* Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
* Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
* Metabolic disorders (e.g. Hurler's Syndrome)
* Severe aplastic anemia
* High-Risk Leukemia:
* Acute Myelogenous Leukemia
* Refractory to standard induction therapy (more than 1 cycle required to achieve remission)

  * Recurrent (in CR ≥ 2)
  * Treatment-related AML or MDS
  * Evolved from myelodysplastic syndrome
  * Presence of FLT3 abnormalities
  * FAB M6 or M7
  * Adverse cytogenetics
  * Myelodysplastic Syndrome
  * Acute Lymphoblastic Leukemia including T lymphoblastic leukemia:
  * Refractory to standard induction therapy (time to CR \>4 weeks)
  * Recurrent (in CR ≥ 2)
  * WBC count \>30,000/mcL at diagnosis
  * Age \>30 at diagnosis
* Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL rearrangements.
* Chronic Myelogenous Leukemia in accelerated phase or blast crisis
* Biphenotypic or undifferentiated leukemia
* Burkitt's leukemia or lymphoma
* Lymphoma:
* Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
* Marginal zone or follicular lymphoma that is progressive after at least two prior therapies
* Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT
* Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status
* Adequate organ function:
* Cardiac - LVEF \>45%, or shortening fraction \>25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
* Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
* Renal - serum Cr \< 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
* Hepatic - total bilirubin level \< 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
* Performance Status Karnofsky or Lansky score ≥ 70%.
* Informed Consent must be obtained prior to initiating conditioning therapy.
* Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.

Exclusion Criteria:

* Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
* Autologous HSCT \< 6 months prior to proposed UCB transplant
* Pregnant or breast feeding
* Current uncontrolled infection
* Evidence of HIV infection or positive HIV serology

Primary outcomes:
measure: Engraftment of ANC and Platelets
timeFrame: 42 days following the infusion of stem cells for ANC [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.]
Secondary outcomes:
measure: Rate of non-engraftment and of secondary graft failure
timeFrame: At 30 days, 100 days, 6 months and yearly from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.
measure: Incidence of acute graft-versus-host disease
timeFrame: At 30 days and 100 days after transplant from the date of transplant until the date of documented acute GvHD.
measure: Incidence of chronic graft-versus-host disease
timeFrame: At 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.
measure: Disease-free survival
timeFrame: At 30 days, 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Wilmot Cancer Institute
state: New York
Study officials:
affiliation: Professor - Department of Medicine, Hematology/Oncology (SMD)
name: Omar Aljitawi, MD
role: PRINCIPAL_INVESTIGATOR
References: