Single Treatment With FT1050 of an Ex-vivo Modulated Umbilical Cord Blood Unit

Hodgkin's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01527838
• Other study ID #: FT1050-02
• Status: Completed
• Phase: Phase 1
• First received: February 1, 2012
• Last updated: September 9, 2016
• Start date: January 2012
• Est. completion date: November 2013

Study information

• Verified date: January 2015
• Source: Fate Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Hodgkin Disease
• Hodgkin's Disease
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma (NHL)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Single FT1050 treated UCB unit
Ex-vivo CXCR4 upregulated hematopoietic progenitor cells, cord blood

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute-Hematopoietic Stem Cell Transplant Program	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State Univeristy Comprehensive Cancer Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Fate Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neutrophil engraftment/chimerism	To determine the minimally effective TNC dose for a single FT1050-treated CB unit based on neutrophil engraftment/chimerism when used for hematopoietic reconstitution following a reduced-intensity conditioning regimen for hematologic malignancies.	Day 42	No
Secondary	Safety	Define the safety profile of treatment with a single FT1050-treated CB unit. To define the preliminary efficacy of treatment with a single FT1050-treated CB unit.	Day 100	Yes
Secondary	Immune reconstitution	To assess immune reconstitution (B-, T-, and NK-cells).	2 years	No
Secondary	Donor search	To determine time from the initiation of donor search to transplantation.	Day 0	No