This phase I trial is to find out the best dose and side effects of tegavivint in treating patients with leukemia that has come back (relapsed) or does not response to treatment (refractory). Tegavivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tegavivint in combination with decitabine may help control the disease.
Not yet recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Decitabine | 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine | Treatment (tegavivint, decitabine) |
| Tegavivint | BC 2059, BC-2059, BC2059, Tegatrabetan | Treatment (tegavivint, decitabine) |
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of
tegavivint in patients with relapsed and refractory acute myeloid leukemia (AML). (Phase I
dose escalation) II. To determine the maximum tolerated dose (MTD) and dose limiting
toxicities (DLT) of tegavivint combined with decitabine in patients with relapsed and
refractory acute myeloid leukemia (AML). (Combination cohort)
SECONDARY OBJECTIVES:
I. To assess the safety profile of tegavivint as characterized by adverse event (AE) type,
severity, timing and relationship to study drug, as well as laboratory abnormalities in the
first and subsequent treatment cycles. (Phase I dose escalation) II. To explore the efficacy
(complete remission [CR], complete remission without blood count recovery [CRi], or partial
remission [PR], of tegavivint as a single-agent in patients with relapsed/refractory (R/R)
AML. (Phase I dose escalation) III. To assess overall survival (OS), and disease-free
survival (DFS) in patients with R/R AML treated with tegavivint. (Phase I dose escalation)
IV. To assess the duration of disease control defined as first date of disease control
identified (either CR/CRi, PR or SD) until the date of progression. (Phase I dose escalation)
V. To explore biomarkers of response and resistance in patients with R/R AML treated with
tegavivint. (Phase I dose escalation) VI. To assess the safety profile of tegavivint in
combination with decitabine as characterized by adverse event (AE) type, severity, timing and
relationship to study drug, as well as laboratory abnormalities in the first and subsequent
treatment cycles. (Combination cohort) VII. To explore the efficacy (complete response [CR],
complete response without blood count recovery [CRi], or partial response [PR], of tegavivint
in combination with decitabine in patients with R/R AML. (Combination cohort) VIII. To assess
overall survival (OS), and disease free survival (DFS) in patients with R/R AML treated with
tegavivint + decitabine. (Combination cohort) IX. To assess the duration of disease control
defined as first date of disease control identified (either CR/ CRi, PR or SD) until the date
of progression. (Combination cohort) X. To explore biomarkers of response and resistance in
patients with R/R AML treated with tegavivint + decitabine. (Combination cohort)
OUTLINE: This is a dose-escalation study.
PART I: Patients receive tegavivint intravenously (IV) over 4 hours on days 1, 8, 15, and 22.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART II: Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 and decitabine
IV over 30-60 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Treatment (tegavivint, decitabine) | Experimental | PART I: Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. PART II: Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 and decitabine IV over 30-60 minutes on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
Inclusion Criteria:
- Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R)
acute myeloid leukemia for which no available standard therapies are indicated or
anticipated to result in a durable response
- Age >= 18 years
- Patients must not have had leukemia therapy for 14 days prior to starting tegavivint
(BC-2059). However, patients with rapidly proliferative disease may receive
hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and
during the first cycle of study
- Bilirubin =< 2.5 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper
limit of normal (ULN) - or =< 5 x ULN if related to leukemic involvement
- Creatinine =< 1.5 x ULN
- Known cardiac ejection fraction of > or = 45% within the past 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- A negative urine pregnancy test is required within 1 week for all women of
childbearing potential prior to enrolling on this trial
- Patient must have the ability to understand the requirements of the study and signed
informed consent. A signed informed consent by the patient or his legally authorized
representative is required prior to their enrollment on the protocol
Exclusion Criteria:
- Pregnant women are excluded from this study because the agent used in this study has
the potential for teratogenic or abortifacient effects. Because there is a potential
risk for adverse events in nursing infants secondary to treatment of the mother with
the chemotherapy agents, breastfeeding should also be avoided
- Uncontrolled intercurrent illness including, but not limited to active uncontrolled
infection, symptomatic congestive heart failure (New York Heart Association [NYHA]
class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia,
or psychiatric illness/social situations that would limit compliance with study
requirements
- Patient with documented hypersensitivity to any of the components of the therapy
program
- Patients with active, uncontrolled central nervous system (CNS) leukemia will not be
eligible
- Men and women of childbearing potential who do not practice contraception. Women of
childbearing potential and men must agree to use at least 1 form of barrier birth
control (such as condom) prior to study entry and for the duration of study
participation
- Prior treatment with tegavivint
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Incidence of adverse events |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | Adverse events will be tabulated with frequency and percentage by grade, attribution to treatment, and by dose level/schedule. |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | M.D. Anderson Cancer Center |
May 5, 2021
