Clinical trial NCT01527838: Single Treatment With FT1050 of an Ex-vivo Modulated Umbilical Cord Blood Unit
Official title: A Phase I Trial of a Single FT1050 (16,16-Dimethyl Prostaglandin E2) Ex Vivo-Modulated Umbilical Cord Blood (CB) Unit Following a Reduced Intensity Conditioning Regimen For Adults With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma (NHL)
Hodgkin's Disease
Chronic Lymphocytic Leukemia (CLL)
Acute Myelogenous Leukemia (AML)
Acute Lymphoblastic Leukemia (ALL)
Keywords: Hematologic malignancies
Lead sponsor: Fate Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-02-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is a prospective, open-label, single-arm trial of the safety of a single FT1050-treated CB unit for hematopoietic reconstitution after a reduced-intensity conditioning regimen for hematologic malignancies. A maximum of 40 eligible adult subjects will be enrolled and treated in the trial at approximately 2-4 centers within the U.S.

Detailed description: The trial will be conducted in three sequential cohorts of 6-12 evaluable subjects each.

Cohort 1 will enroll eligible subjects for whom a single CB unit has been identified that meets the minimum HLA-matching criteria and has a minimum pre-cryopreservation total nucleated cell (TNC) dose of at least 2.5 x 10\^7 cells/kg. Cohort 2 is identical to Cohort 1, except that the TNC dose of the CB unit must be between 2.0 - \<2.5 x 10\^7 cells/kg. Finally, Cohort 3 is identical to Cohort 2, except that the TNC dose of the CB unit must be between 1.5 - \<2.0 x 10\^7 cells/kg. If no safety rules are triggered, the study will proceed to the next dosing cohort. Within a dosing cohort, no more than three subjects may be before Day 42 at any one time, unless they have already engrafted neutrophils. The final dosing cohort is defined as the last cohort where 12 evaluable subjects are treated and no stopping rules are triggered. The corresponding TNC dose level will be considered the minimally acceptable TNC dose level.

Eligibility criteria: Inclusion Criteria:

1. Subjects with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate. Eligible diseases and stages include:

   * Non-Hodgkin's lymphoma or Hodgkin's lymphoma
   * Chronic lymphocytic leukemia (CLL)
   * Acute myelogenous leukemia (AML)
   * Chronic myelogenous leukemia (CML)
2. Lack of 5-6/6 HLA-matched related or 8/8 HLA-A, B, C, DRß1 matched unrelated donor; or unrelated donor not available within appropriate timeframe.

   * Identification of suitable backup CB unit(s) (single unit with pre-cryopreservation cell dose ≥ 2.5 x 10\^7 TNC/kg or two units with pre-cryopreservation cell dose ≥ 1.5 x 10\^7 TNC/kg each) and meeting minimum HLA match criteria.
   * An acceptable alternative to one or two backup CB unit(s) is the identification of an eligible related haploidentical donor that meets minimum HLA match criteria.
3. Age 18-65 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
5. Signed IRB approved Informed Consent Form (ICF).

Exclusion Criteria:

1. The following hematologic malignancies are excluded:

   * Myelofibrosis (Agnogenic Myeloid Metaplasia)
   * Aplastic anemia.
2. Previous treatment that included an allogeneic transplant
3. Cardiac disease: symptomatic congestive heart failure or evidence of left ventricular
4. dysfunction (Ejection fraction \< 40%) as measured by gated radionucleotide ventriculogram or echocardiogram; active angina pectoris, or uncontrolled hypertension; history of myocardial infarction with depressed ejection fraction.
5. Pulmonary disease: symptomatic chronic obstructive lung disease, symptomatic restrictive lung disease, or corrected DLCO of \< 50% of predicted, corrected for hemoglobin.
6. Renal disease: serum creatinine \> 2.0 mg/dl and calculated creatinine clearance \< 40 mL/min
7. Hepatic disease: serum bilirubin \> 2.0 mg/dl (except in the case of Gilbert's syndrome or ongoing hemolytic anemia), SGOT or SGPT \> 3 x upper limit of normal.
8. Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation.
9. HIV antibody.
10. Uncontrolled infection.
11. Pregnancy or breast feeding mother.
12. Inability to comply with the requirements for care after allogeneic stem cell transplantation.
13. Participation in a concurrent clinical trial with a novel, unapproved investigational agent \< 30 days prior to Day 0.

Primary outcomes:
measure: Neutrophil engraftment/chimerism
timeFrame: Day 42
Secondary outcomes:
measure: Safety
timeFrame: Day 100
measure: Immune reconstitution
timeFrame: 2 years
measure: Donor search
timeFrame: Day 0
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute-Hematopoietic Stem Cell Transplant Program
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State Univeristy Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Fate Therapeutics
name: Samuel Dychter, MD
role: STUDY_DIRECTOR
References: