Clinical Trial 18390

Cancer Type: Malignant Hematology
Interventions:FT-1101

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Jeffrey Lancet

Overview

Study Title

A Phase 1 Dose Escalation, Multicenter, Open-Label, Safety, Pharmacokinetic and Pharmacodynamic Study of FT-1101 In Patients With Relapsed or Refractory Hematologic Malignancies

Summary

The major purposes of this study are to determine the maximum dose of FT-1101 (study drug or the investigational drug) that can be tolerated, and once this dose is found, if it has any effect in patients with acute leukemia or myelodysplastic syndrome.

Objective

Primary: To determine the maximum tolerated dose (MTD), the dose limiting toxicities (DLT), and the FT-1101 dose recommended for future phase 2 studies (RP2D) for patients with relapsed refractory acute leukemia or high-risk myelodysplastic syndrome (MDS). Secondary: To determine the pharmacokinetics (PK) of FT-1101. To observe patients for any evidence of anti-leukemic or antimyelodysplastic activity of FT-1101, as determined by changes in complete blood count/differential bone marrow histology and physical exam.

Inclusion Criteria

  • For AML/MDS Treatment Cohort dose escalation: Histologically or cytologically proven acute myelogenous leukemia or high-risk MDS as defined by the World Health Organization (WHO) criteria and IPSS-R, respectively, that is relapsed or refractory to standard therapy or for whom standard treatments are contraindicated. A.) AML expansion group only: histologically or cytologically proven acute myelogenous leukemia as defined by WHO criteria, that is relapsed or refractory to standard therapy or for whom standard treatments are contraindicated. B.) MDS expansion group only: histologically or cytologically proven high risk MDS as defined by the IPSS-R, that is relapsed or refractory to standard therapy or for whom standard treatments are contraindicated.
  • For NHL Treatment Cohort dose escalation: Mature B-cell non-Hodgkin lymphomas as defined by WHO (2008) with the following histologies: follicular, marginal zone (splenic, nodal, and extranodal), mantle cell, primary mediastinal, diffuse large B-cell (DLBCL, including Richter's transformation and follicular grade 3b) lymphomas, and B-cell lymphomas not specified (with features of DLBCL/Burkitt's lymphoma) that is relapsed or refractory to standard therapy and for whom standard treatments are contraindicated or unavailable . A.) Indolent NHL expansion group only: Mature B-cell non-Hodgkin lymphomas as defined by WHO (2008) with the following histologies: follicular, small lymphocytic, marginal zone (splenic, nodal, and extranodal), and mantle cell lymphomas. B.) Aggressive NHL expansion group only: Mature B-cell non-Hodgkin lymphomas as defined by WHO (2008) with the following histologies: primary mediastinal lymphoma, DLBCL (including Richter's transformation and follicular Grade 3b), and B-cell lymphomas not specified (with features of DLBCL/Burkitt's lymphoma).
  • For NHL Treatment Cohort (dose escalation and expansion) only: A.) Adequate bone marrow function defined by ANC ≥ 750 cells/mm^3, platelet count ≥ 75,000/mm^3, and hemoglobin ≥ 8 g/dL at screening. Note: Patients who are on chronic red blood cell (RBC) transfusions or erythropoietin to maintain a hemoglobin (Hgb) ≥ 8 g/dL are eligible. B.) Measurable lymph node or tumor mass ≥ 1.5 cm in at least 1 dimension by CT or MRI requiring treatment at the discretion of the investigator.
  • Age 18 years and older
  • Adequate kidney and liver function
  • No prior organ allograft
  • For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 90 days after study treatment

  • Exclusion Criteria

  • History of prior malignancy unless disease free for > 2 years.
  • Patients with symptomatic central nervous system (CNS) metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy
  • Treatment with major surgery (requiring general anesthesia) within one month prior to study entry
  • Previous treatment with any prior Bromodomain and Extra-Terminal family (BET) inhibitor therapy
  • Unable to swallow oral medications, or patients with gastrointestinal conditions (e.g., malabsorption, gastric or small bowel resection, etc.) deemed to jeopardize intestinal absorption
  • Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
  • Pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD), asthma, etc.) that is not controlled (moderate to severe symptoms) with current medication
  • Known HIV positivity
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Baseline QTcF > 480 msec (average of QTcF values from screening triplicate ECGs). NOTE: This criterion does not apply to patients with a left bundle branch block.
  • Concurrent treatment with any agent known to prolong the QTc interval