Safety and Early Efficacy Study of TBX-2400 in Patients With AML or Myelofibrosis

• ClinicalTrials.gov Identifier: NCT04709458
• Recruitment Status: Not yet recruiting
• First Posted: January 14, 2021
• Last Update Posted: May 3, 2022
• Sponsor: Taiga Biotechnologies, Inc.
• Information provided by (Responsible Party): Taiga Biotechnologies, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myelofibrosis; Acute Myelogenous Leukemia	Biological: TBX-2400	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: September 1, 2022
• Estimated Primary Completion Date: August 28, 2024
• Estimated Study Completion Date: October 28, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: TBX-2400 treatment; Single intravenous infusion of TBX-2400	Biological: TBX-2400; Hematopoietic stem cells transplantation

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events according to NCI-CTCAE Version 5.0 [ Time Frame: Two years ]
   Adverse events from subject reporting or other assessments
2. Transplant engraftment [ Time Frame: 1 year ]
   Assessment of transplant engraftment will include absolute neutrophil count, untransfused platelet count and donor chimerism

Secondary Outcome Measures :

1. Immune reconstitution as measured by CD3+ cell count [ Time Frame: Up to Day 360 ]
   Immune reconstitution as measured by CD3+ cell count > 300/μL
2. Immunoglobulin (IgA) levels [ Time Frame: Up to Day 360 ]
3. Immunoglobulin (IgM) levels [ Time Frame: Up to Day 360 ]
4. T-cell Engraftment [ Time Frame: Up to Day 360 ]
   CD45 RA versus RO at 3, 6, 9 and 12 months
5. Disease-free survival [ Time Frame: Two years ]
6. Incidence of secondary graft failure [ Time Frame: Two years ]
7. Transplant-Related Mortality (TRM) [ Time Frame: 100 Days ]
8. Quality of life using the World Health Organisation Five Wellbeing Index [ Time Frame: Up to day 360 ]
   QoL assessed at 3, 6, 9 and 12 months (World Health Organization [WHO] Five Wellbeing Index).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Vivienne Margolis, B.Sc; +972-4639634; vmargolis@taigabiotech.com

Contact: Yosef Refaeli, Ph.D; +1-720-859-3547; refaeli@taigabiotech.com

Locations

Croatia

University Hospital Centre Zagreb

Zagreb, Croatia, 10000

Contact: Nadira Durakovic, MD, PhD +385-989611829 nadira.durakovic@mef.hr

Principal Investigator: Nadira Durakovic, MD, PhD

Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy, 00168

Contact: Simona Sica, MD TBA Simona.sica@unicatt.it

Principal Investigator: Simona Sica, MD

Sponsors and Collaborators

Taiga Biotechnologies, Inc.

Investigators

• Principal Investigator: Andrea Bacigalupo, MD; Unit for Hematology and BMT, Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy

More Information

• Responsible Party: Taiga Biotechnologies, Inc.
• ClinicalTrials.gov Identifier: NCT04709458
• Other Study ID Numbers: TBX-2400-001
• First Posted: January 14, 2021
• Last Update Posted: May 3, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Taiga Biotechnologies, Inc.:

Myelofibrosis; Leukemia; Allogeneic stem cell transplant; Acute Myelogenous Leukemia; Myeloproliferative disorders; Primary myelofibrosis; Bone Marrow Cancer; Bone Marrow Transplant; Acute Myeloid Leukemia

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Primary Myelofibrosis; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases