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

Phase 1

Completed

• Conditions: Hodgkin's Disease; Acute Myelogenous Leukemia (AML); Chronic Lymphocytic Leukemia (CLL); Non-Hodgkin's Lymphoma (NHL); Acute Lymphoblastic Leukemia (ALL)
• Interventions: Biological: Single FT1050 treated UCB unit

• Registration Number: NCT01527838
• Lead Sponsor: Fate Therapeutics

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.

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-02-01
• Study First Submitted QC: 2012-02-03
• Study First Posted: 2012-02-07
• Primary Completion: 2013-10
• Study Completion: 2013-11
• Status Verified: 2015-01
• Last Update Submitted: 2016-09-09
• Last Update Posted: 2016-09-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single FT1050 treated UCB Unit	Single FT1050 treated UCB unit	Ex-vivo CXCR4 upregulated hematopoietic progenitor cells, cord blood

Primary Outcome Measures

Name	Time	Method
Neutrophil engraftment/chimerism	Day 42	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.

Secondary Outcome Measures

Name	Time	Method
Safety	Day 100	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.
Immune reconstitution	2 years	To assess immune reconstitution (B-, T-, and NK-cells).
Donor search	Day 0	To determine time from the initiation of donor search to transplantation.

Trial Locations

Locations (3)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute-Hematopoietic Stem Cell Transplant Program; 🇺🇸 Boston, Massachusetts, United States

Ohio State Univeristy Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States