A Phase 1 trial to Investigate the Safety, Pharmacokinetic Profiles and the Efficacy of Tinostamustine, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies.

Recruiting

• Conditions: relapsed or refractory lymphoid malignancy, relapsed/refractory multiple myeloma, relapsed/refractory Hodgkins lymphoma, relapsed/refractory peripheral T-cell lymphoma, relapsed/refractory cutaneous T-cell lymphoma, subtypes mycosis fungoides and Sézary syndrome, relapsed/refractory T-cell Prolymphocytic leukemia. Note: Recruitment to the CTCL and T-PLL cohorts was halted on 01 March 2021.; Relapsed/ refractory Hematologic Malignancies; 10025319

• Registration Number: NL-OMON52700
• Lead Sponsor: Mundipharma Research Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 10

Inclusion Criteria

1. Patient willing and able to sign an informed consent.
2. Patients age >=18 years at signing the informed consent.
3. Life expectancy > 3 months.
4. Diagnosis of relapsed or refractory lymphoid malignancy for which there are
no available therapies.
5. Eastern Cooperative Oncology Group (ECOG) performance status <=2.
6. Absolute neutrophil count (ANC) (polymorphonuclear [PMN] cells plus
bands) >1,000 / µL.
7. Platelets >= 100,000 / µL.Platelet transfusions within the 14 days before Day
1 of Cycle 1 is prohibited.
8. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <= 2.5 x ULN.
9. Total bilirubin <2.0 mg/dL unless elevated due to known Gilbert's syndrome.
10. Renal function: estimated creatinine clearance by Cockroft-Gault
formula >= 45 mL/min.
11. Serum potassium and magnesium at least at the lowest limit of normal (LLN)
range, before every IMP administration; if it is below LNN, supplementation is
permissible.
12. Female study participants of childbearing potential, and their
partners, and male study participants who intend to be sexually active with a
woman of childbearing potential, must be willing to use at least TWO
highly effective forms of contraception. For female study participants,
this should start from the time of study enrollment and continue
throughout tinostamustine administration and for at least six months
after the last administration of IMP to be eligible to participate. For male
subjects who intend to be sexually active with a women of childbearing
potential they must use a condom during treatment and for at least 90
days after the last administration of IMP. Female study participants
should be willing to have a pregnancy test performed at screening, <= 1
day prior to day 1 of each IMP administration and at study treatment
discontinuation. Vasectomized males are considered fertile; therefore,
vasectomized partners and patients must be willing to use a secondary
method of effective birth control. Sexual abstinence is considered a
highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study
treatment. The reliability of sexual abstinence needs to be evaluated in
relation to the duration of the clinical trial and the preferred and usual
lifestyle of the patient.

Apart from the above general inclusion criteria, there are some criteria that
are specific for each cohort, see details in the protocol.

Exclusion Criteria

1. Patients with any central nervous system (CNS) involvement.
2. Patient who had a hematologic malignancy that has transformed.
3. Patients who have relapsed within 100 days of stem cell infusion following an
autologous or allogeneic bone marrow transplant.
4. Patients with QTc interval (Fridericia*s formula) > 450 msec.
5. Patients who are on treatment with drugs known to prolong the
QT/QTc interval. Refer to CredibleMeds list of drugs with known risk of
Torsade de pointes (TdP): http://crediblemeds.org
6. Any serious medical condition that interferes with adherence to
study procedures.
7. Patients with a history of an other malignancy diagnosed within
three (3) years prior to study enrollment excluding basal cell carcinoma
of the skin, squamous cell carcinoma of the skin, or in situ cervical
cancer that has undergone potentially curative therapy.
8. Pregnant or breast feeding females.
9. New York Heart Association (NYHA) stage III/IV congestive heart
failure. The following arrhythmias: atrial fibrillation/flutter with poor rate
control, documented sustained ventricular tachycardia (defined as >30 seconds
or requiring cardioversion before 30 seconds have elapsed) or Torsades de
Pointes.
10. active infections, or other significant co-morbidities [e.g. active
central nervous system metastases and/or carcinomatous meningitis,
active infection requiring systemic therapy, history of human
immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis
C].
11. Use of other anti cancer therapies and investigational agents within 28
days prior to the first dose of tinostamustine. After 28 days, patients may be
enrolled if they have recovered form any related toxicities >= Grade 1 (except
alopecia).
12. Steroid treatment within seven days prior to trial treatment. Patients that
require intermittent use of bronchodilators, topical steroids or local
steroid injections will not be excluded from the trial. Patients who have
been stabilized to 10 mg orally (PO) once daily (QD) or less seven days
prior to tinostamustine administration are allowed.
13. Patients on Valproic Acid for any indication (epilepsy, mood disorder)
must be excluded from the trial.

Study & Design

• Study Type: Interventional
• Study Design: Not specified