Safety and Tolerability of HSC835 in Patients With Hematological Malignancies

A First-in-human, Single-arm, Single-center, Open-label, Proof-of-concept Study to Evaluate the Safety and Tolerability of Infusing HSC835 (LFU835-expanded Umbilical Cord Blood Hematopoietic Stem Cells) in Patients With Hematological Malignancies

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01474681

Enrollment

Registered

2011-11-18

Start date

2012-01-09

Completion date

2016-10-03

Last updated

2020-12-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Lymphocytic Leukemia, Acute Myelocytic Leukemia, Burkitt's Lymphoma, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Follicular Lymphomas, High Grade Lymphomas, Large-cell Lymphoma, Lymphoblastic Lymphoma, Lymphoplasmacytic Lymphoma, Mantle-cell Lymphoma, Marginal Zone Lymphoma, Myelodysplastic Syndrome

Keywords

hematologic malignancies, leukemia, lymphoma

Brief summary

This study evaluated the safety and tolerability of using HSC835 in patients with hematological malignancies.

Interventions

BIOLOGICALHSC835

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

10 Years to 55 Years

Healthy volunteers

Inclusion criteria

* Patients with a diagnosis that qualifies them for a DUCBT * Absence of recent active mold infection * Adequate organ function * Availability of eligible donor material

Exclusion criteria

* Pregnancy or breastfeeding women and women of child-bearing potential unless two acceptable forms of contraception are being used * Human immunodeficiency virus (HIV) infection * Active infection * Extensive prior chemotherapy * Prior myeloablative allotransplantation or autologous transplant.

Design outcomes

Primary

Measure	Time frame	Description
Safety and Tolerability of HSC835 for Clinical Use Were Measured by Infusional Toxicity (Within First 48 Hours After Transplant) and Absence of Graft Failure After 32 Days in Excess of That Currently Observed With UCBT.	32 days	The safety and tolerability of HSC835 for clinical use were measured by infusional toxicity and absence of graft failure in excess of that currently observed with UCBT. Infusional toxicity - AE from transplant until first 48 hours. Administration of the HSC835 expanded CD34-positive cell product, infused over a period of approximately 15 minutes may theoretically cause adverse reactions based on hemodynamic effects, the release of factors like cytokines through administration into the systemic circulation, or acute hypersensitivity, among others.

Secondary

Measure	Time frame	Description
Incidence of Platelet Recovery Within Six Months	6 months	Incidence of platelet recovery within six months. Number of participants recovering platelet to ≥50,000 × 109/L for at least one week without transfusion in the prior 7 days to the first measurement.
Frequency of Expanded Unit Predominance at Day 100 (DUCBT Recipients Only)	Day 100	Frequency of expanded unit predominance at day 100 (DUCBT recipients only) unit predominance was assessed by differences in microsatellite patterns between the recipient, HSC835 and the unmanipulated cord blood unit. Evaluation of sorted CD15-positive/CD33-positive myeloid and CD3-positive T cells in the peripheral blood, revealed three patterns: predominance of HSC835, Mixed dominance an unique chimerism pattern was observed with the CD15/CD33 population predominantly derived from HSC835 and the CD3 population almost exclusively derived from the unmanipulated unit, and predominance of the unmanipulated unit
Incidence of Transplant Related Mortality (TRM) Within 100 Days and One Year	Day 100 and Month 12	Number of participants with incidence of transplant related mortality (TRM) within 100 days and one year
Incidence of Neutrophil Recovery Within 42 Days	42 days	Neutrophil recovery (engraftment) is defined as the first of three consecutive days with ANC \> 0.5 x 109/L which occurred for all patients before 42 days post transplant.
Incidence of Relapse Within One Year	Month 12	Number of participants with Incidence of relapse within one year
Overall Survival (OS) Within One Year	Month 12	Number of participants with Overall survival (OS) within one year
Disease Free Survival (DFS) Within One Year	Month 12	Number of participants with Disease Free Survival (DFS) within one year. Patients are considered to have achieved DFS or relapse-free survival if they had not experienced either relapse or death (of any cause)
Incidence of Acute Graft Versus Host Disease (aGVHD) Within 100 Days and Chronic Graft Versus Host Disease (cGVHD) Within 1 Year	Day 100 and Monnth 12	Number of participants with incidence of Acute Graft Versus Host Disease (aGVHD) within 100 days and Chronic Graft Versus Host Disease (cGVHD) within 1 year

Countries

United States

Participant flow

Recruitment details

Single arm study of HSC835 broken down into 4 subgroups for analyses and 6 subgroups for safety.

Participants by arm

Arm	Count
SUCBT Single umbilical cord blood transplant (SUCBT) This is the combination of the SUCBT\<18 yrs and SUCBT \>= 18 yrs	9
DUCBT Double umbilical cord blood transplant (DUCBT) This is the combination of the DUCBT\<18 yrs and DUCBT \>= 18 yrs	18
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Death	0	3	2	6

Baseline characteristics

Characteristic	SUCBT	DUCBT	Total
Age, Continuous	33.3 years STANDARD_DEVIATION 17.18	31.3 years STANDARD_DEVIATION 13.75	32.0 years STANDARD_DEVIATION 14.67
Sex: Female, Male Female	5 Participants	6 Participants	11 Participants
Sex: Female, Male Male	4 Participants	12 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	1 / 1	8 / 8	3 / 3	15 / 15	9 / 9	18 / 18
serious Total, serious adverse events	1 / 1	7 / 8	3 / 3	14 / 15	8 / 9	17 / 18

Outcome results

Primary

Safety and Tolerability of HSC835 for Clinical Use Were Measured by Infusional Toxicity (Within First 48 Hours After Transplant) and Absence of Graft Failure After 32 Days in Excess of That Currently Observed With UCBT.

The safety and tolerability of HSC835 for clinical use were measured by infusional toxicity and absence of graft failure in excess of that currently observed with UCBT. Infusional toxicity - AE from transplant until first 48 hours. Administration of the HSC835 expanded CD34-positive cell product, infused over a period of approximately 15 minutes may theoretically cause adverse reactions based on hemodynamic effects, the release of factors like cytokines through administration into the systemic circulation, or acute hypersensitivity, among others.

Time frame: 32 days