Clinical trial NCT04709458: Safety and Early Efficacy Study of TBX-2400 in Patients With AML or Myelofibrosis
Official title: A Phase I Study to Assess the Safety and Early Efficacy of TBX-2400 in Enhancing Engraftment in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Acute Myelogenous Leukemia or Myelofibrosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Myelofibrosis
Acute Myelogenous Leukemia
Keywords: Myelofibrosis
Leukemia
Allogeneic stem cell transplant
Acute Myelogenous Leukemia
Myeloproliferative disorders
Primary myelofibrosis
Bone Marrow Cancer
Bone Marrow Transplant
Acute Myeloid Leukemia
Lead sponsor: Taiga Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study of allogeneic stem cell transplantation with TBX-2400 in adult subjects with Acute Myelogenous Leukemia (AML) or Myelofibrosis (MF).

The donor cells are exposed to a protein that has been shown in the laboratory to improve the ability of the donor cells to make blood and immune cells after transplant. Exposure of the donor cells to this protein does not modify the genes in the cells in any way.

This study has two goals. The first goal is to find out if transplant with TBX-2400 is safe. The second goal is to find out what effects TBX-2400 stem cells have on time to engraftment in adult subjects with AML or MF.

The study hypothesis is that TBX-2400 cells will shorten the time to immune reconstitution after transplant.


Eligibility criteria: Inclusion Criteria:

1. For crAML: AML with ≥5% blasts (either by morphology or by multi-parameter flow cytometry \[MFC\]) in a marrow aspirate obtained within 21 days of enrollment in the trial, and following the administration of at least two prior courses of chemotherapy;
2. For MF: primary MF or MF that has progressed from a myeloproliferative disease. Dynamic International Prognostic Scoring System (DIPSS)-plus to be utilized to support the inclusion of MF subjects at screening;
3. Subject undergoing allogeneic stem cell transplantation on the decision of transplanting physician;
4. Signed informed consent of donor and recipient;
5. Subjects of ≥ 18 years of age (no upper age limit);
6. Donor agrees to donate bone marrow-derived or mobilized peripheral blood stem cells;
7. Subjects with Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2;
8. Adequate pulmonary function with Diffusing Capacity for Carbon Monoxide (DLCO) \> 50;
9. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception (e.g. sterilization, hormone implants, hormone injections, intrauterine devices, or vasectomized partner with combined use of condom and/or birth control pills) from screening until 6 months after TBX-2400 transplantation;
10. Able to adhere to all trial treatments and procedures.

Exclusion Criteria:

1. Previous stem cell transplantation;
2. For MF: Blasts \> 10% in a marrow aspirate obtained within 30 days of screening;
3. Renal function: serum creatinine \> 1.5 x Upper Limit of Normal (ULN);
4. Hepatic function: impaired synthetic function as indicated by a serum fibrinogen below the normal limit. Aspartate transaminase/alanine transaminase (AST/ALT) \> 3.0 x ULN. Bilirubin, \> 1.5 x ULN;
5. Cardiac function: ejection fraction \< 45% as determined by echocardiography;
6. Prior malignancy active within previous three years - except for locally curable cancers such as cutaneous basal or squamous cell cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, or carcinoma in situ of the prostate;
7. Positive pregnancy test or breastfeeding for women of childbearing age;
8. Serologic evidence of chronic Hepatitis B virus infection or Hepatitis C exposure;
9. Known history of positive test for Human Immunodeficiency Virus (HIV) or known Acquired Immunodeficiency Syndrome (AIDS);
10. Hypersensitivity to any trial medication (including the preparative regimen, TBX-2400 treatment and any prophylaxis or other medication planned);
11. Presence of a serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with trial participation or trial drug administration, impair the ability of the participant to receive protocol therapy, or interfere with interpretation of trial results.

Primary outcomes:
measure: Incidence of adverse events according to NCI-CTCAE Version 5.0
timeFrame: Two years
measure: Transplant engraftment
timeFrame: 1 year
Secondary outcomes:
measure: Immune reconstitution as measured by CD3+ cell count
timeFrame: Up to Day 360
measure: Immunoglobulin (IgA) levels
timeFrame: Up to Day 360
measure: Immunoglobulin (IgM) levels
timeFrame: Up to Day 360
measure: T-cell Engraftment
timeFrame: Up to Day 360
measure: Disease-free survival
timeFrame: Two years
measure: Incidence of secondary graft failure
timeFrame: Two years
measure: Transplant-Related Mortality (TRM)
timeFrame: 100 Days
measure: Quality of life using the World Health Organisation Five Wellbeing Index
timeFrame: Up to day 360
Other outcomes:
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
Study officials:
affiliation: Unit for Hematology and BMT, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
name: Andrea Bacigalupo, MD
role: PRINCIPAL_INVESTIGATOR
References: