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Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia

Phase 1
18 Years
Not Enrolling
Lymphoma, Acute Lymphocytic Leukemia

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Trial Information

Phase 1, Dose Escalation Study To Assess the Safety, Pharmacokinetics and Activity of 2-Hour Continuous Intravenous Dosing of ON 013105 Administered Weekly in Patients With Relapsed/Refractory Lymphoma and Acute Lymphoid Leukemia

This is an open-label, dose-escalation Phase I study of ON 013105 in patients with
relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome
negative) who have satisfied all inclusion/exclusion criteria. Patients will receive weekly
2-hour IV infusions of ON 013105, until evidence of disease progression, intolerable adverse
events, or withdrawal of patient consent. Up to 12 additional patients will be treated at
the RPTD level. The starting dose will be 17 mg over a 2-hour weekly infusion. Each cycle
will comprise three weeks.

Up to 43 patients may be enrolled, of which approximately 7 to 37 patients will be enrolled
in the dose escalation portion of the study to determine the RPTD. After the maximally
administered dose is attained and at least six patients have received a tentative RPTD, up
to 6 additional patients may be enrolled in the dose confirmation phase to confirm the RPTD

Treatment will be administered in the Clinical Research center for the first dose for all
patients at each given dose level. If there is no toxicity, then subsequent doses at that
level for that patient may be administered on an outpatient basis, unless hospitalization is
required for another reason.

According to the Simon accelerated titration design, one-patient cohorts and 100% dose
increments will be implemented until non-hematological grade 2 toxicity is observed during
the first 3-week cycle. The design will then convert to standard 3/6 patient cohorts
starting at the dose level where grade 2 toxicity was observed and following 40% dose
increments for the subsequent cohorts.

If none of the first three patients experiences a dose-limiting toxicity (DLT) during the
first cycle (3 weeks), the next 3 patients will receive the next dose level. If there is a
DLT in one of the first three patients, this dose level will be expanded to 6 patients. If 1
patient out of 6 experiences DLT, the next patients will receive the next dose level. If ≥ 2
patients experience DLT at any dose level, this dose level will be declared the Maximally
Administered Dose. The Maximally Tolerated Dose (MTD) and RPTD will be the highest dose
level below the Maximally Administered Dose with 0 out of 3 patients or one out of 6
patients with DLT. Dosing will be reduced to the immediate lower dose for any patient who
experiences a DLT at any time.

If Grade 1 non-hematological toxicity occurs, treatment will be continued at the original
dose without dose reduction.

Patients with stable disease or response can continue treatment up to eight 3-week cycles.
Further continuation will be determined by the clinical judgment of the Investigator.
Patients who drop out for any reason may not re-enter the trial.

Blood samples will be collected during Day 1 of the first cycle for pharmacokinetic
assessment. Responses will be assessed according to Cheson, B.D., et al., Revised Response
Criteria for Malignant Lymphoma, J Clin Oncol 2007. 25: p. 579-86.

Inclusion Criteria:

- ≥ 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

Exclusion Criteria:

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Jennifer Cultrera, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

January 2015

Related Keywords:

  • Lymphoma
  • Acute Lymphocytic Leukemia
  • Lymphoma
  • B-cell Acute Lymphocytic Leukemia
  • ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma



H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612