Safety Study of ON 013105 in Lymphoma and Acute Lymphoid Leukemia

NCT01049113 | Terminated Phase 1

• 1 other identifier: ON-013105-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, dose-escalation Phase 1 study of the investigational agent, ON 013105. In laboratory animal studies, ON 013105 has demonstrated anti-cancer activity. The purpose of this study is to determine the highest dose of ON 013105 that can be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). Patients will receive weekly 2-hour IV infusions of ON 013105 at higher and higher doses until intolerable side effects are observed. It is important to know the highest safe dose so additional studies can be done.

Conditions

Lymphoma; Acute Lymphocytic Leukemia

Keywords

Lymphoma; B-cell Acute Lymphocytic Leukemia; ALL

Outcome Measures

Primary Outcomes (1)

• Safety based on adverse events, hematology and chemical laboratory values, urinalysis, coagulation, ECG, vital signs, physical examination.

  2 years

Secondary Outcomes (2)

• Tumor response (according to Cheson, B.D., et al., Revised Response Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86).

  2 years

• Non-compartmental pharmacokinetic analysis of drug concentrations in plasma including area under concentration time curve, half-life, clearance.

  Day 1 of first cycle

Study Arms (1)

ON 013105

EXPERIMENTAL

ON 013105 administered intravenously as 2-hour infusion once a week for 3 weeks of 3-week cycles. This is dose escalation study; starting dose is 17 mg.

Drug: ON 013105

Interventions

ON 013105 DRUG

2-hour intravenous infusion once a week. Starting dose is 17 mg. Maximum dose will be 1525 mg.

Also known as: briciclib

ON 013105

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Documented (cytologically confirmed) relapsed/ refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative)
• ECOG Performance Status score of 0, 1, or 2 (see Attachment 1)
• Expected survival, in the opinion of the Investigator, of at least 3 months, to allow a sufficient observation period for evaluation of ON 013105
• Recovery to at least grade I from adverse effects of prior therapies
• Adequate contraceptive \[including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization\] before entry and throughout the study for female patients of reproductive potential
• Female patient with reproductive potential must have a negative serum beta-HCG pregnancy test at screening
• Willing to adhere to the prohibitions and restrictions specified in this protocol
• Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study

You may not qualify if:

• Grade 3 thrombocytopenia (platelets \<50,000/µL) or neutropenia (ANC \<1000/µL) ) except if documented evidence of bone marrow involvement of lymphoma or leukemia contributing to cytopenias.
• Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
• History of HIV-1 seropositivity
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin \> 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT \> 1.5 X ULN
• Serum creatinine \> 1.5 mg/dL or calculated creatinine clearance \< 60 ml/min.
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 Meq/L).
• Women patients who are pregnant or lactating
• Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 4.4).
• Major surgery without full recovery or major surgery within 3 weeks of ON 013105 treatment start.
• Uncontrolled hypertension (defined as a systolic pressure ³ 180 and/or a diastolic pressure ³ 110)
• New onset seizures (within 3 months prior to the first dose of ON 013105) or poorly controlled seizures
• Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy
• Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (2)

• Park IW, Reddy MV, Reddy EP, Groopman JE. Evaluation of novel cell cycle inhibitors in mantle cell lymphoma. Oncogene. 2007 Aug 16;26(38):5635-42. doi: 10.1038/sj.onc.1210350. Epub 2007 Mar 19.

  PMID: 17369860 BACKGROUND

• Prasad A, Park IW, Allen H, Zhang X, Reddy MV, Boominathan R, Reddy EP, Groopman JE. Styryl sulfonyl compounds inhibit translation of cyclin D1 in mantle cell lymphoma cells. Oncogene. 2009 Mar 26;28(12):1518-28. doi: 10.1038/onc.2008.502. Epub 2009 Feb 9.

  PMID: 19198627 BACKGROUND

Related Links

• The Leukemia \& Lymphoma Society

MeSH Terms

Conditions

Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma

Interventions

ON 013105

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Study Officials

• Jennifer Cultrera, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 14, 2010
• Study Start: November 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2015
• Last Updated: December 8, 2015

Record last verified: 2015-12

Locations

US (1)