A Phase 1/2, Single-Arm Study To Assess The Efficacy and Safety Of 5-day Continuous Intravenous Dosing Of ON 01910.Na Administered Every 2 Weeks in Patients With Intermediate-1, Intermediate-2, or High Risk Myelodysplastic Syndrome (MDS)
18 Years
N/A
Both
Myelodysplastic Syndrome
Trial Information
A Phase 1/2, Single-Arm Study To Assess The Efficacy and Safety Of 5-day Continuous Intravenous Dosing Of ON 01910.Na Administered Every 2 Weeks in Patients With Intermediate-1, Intermediate-2, or High Risk Myelodysplastic Syndrome (MDS)
This is a single center, open label, phase 1/2 study in which two to thirty three patients
with Intermediate-1, Intermediate-2, or High risk MDS will receive ON 01910.Na as a
intravenous continuous infusion (IVCI) over 24 hours for 5 consecutive days every 2 weeks.
In the phase 1 component of this trial the maximum tolerated dose of ON1910.Na in patients
with Intermediate-1, Intermediate-2 or High Risk myelodysplastic syndromes will be
determined. A standard "3+3" dose escalation scheme will be followed with up to six
patients treated at the 800 mg/m2/day dose level. Patients will be observed for 2 cycles
before dose escalation occurs. If none of the initial three patients in the 800 mg/m2/day
cohort experience dose-limiting toxicity (DLT), during the first two cycles, then a new
cohort of three patients will be treated at the 1500 mg/m2/day dose level. If none of the
initial three patients in the 1500 mg/m2/day cohort experience DLT during the first two
cycles, three additional patients will be treated at the 1500 mg/m2/day level. If no more
than one of the six patients at the 1500 mg/m2/day dose level experiences a DLT, then that
dose level will be confirmed as the MTD and no further dose escalation will occur.
If one of the three patients in the 800 mg/m2/day cohort experiences DLT during the first
two cycles, then up to three additional patients will be treated at the same dose level.
Escalation to 1500 mg/m2/day will proceed if only one of the six patients experiences DLT at
the 800 mg/m2/day dose level. If two or more patients in the 800 mg/m2/day cohort experience
DLT during the first two cycles, then the maximum tolerated dose (MTD) will have been
exceeded, no further dose escalation will occur, and a full safety review will determine if
further enrollment of patients will proceed.
If the 800 mg/m2/day dose level is under consideration as the MTD (i.e. if ≥ 2 patients
experience DLT at the 1500 mg/m2/day dose level), and only three patients were treated
before escalation to 1500 mg/m2/day, then three additional patients will be accrued. If no
more than one of the six patients at the 800 mg/m2/day dose level experiences a DLT, then
that dose level will be confirmed as the MTD.
Once the phase 1 portion of the study is completed, accrual to the phase 2 portion will
begin. Patients treated at the MTD during the phase 1 portion will be included in the phase
2 component and will be evaluated for response and secondary end points.
The total study duration is 29 weeks, which includes a 2-week screening phase, a 23-week
dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na.
Patients will be assessed for response and will undergo follow up.
Patients who drop out for any reason will not be replaced. Patients who achieve a complete
or partial response or stabilization of their disease by week 25 are eligible to receive an
additional 24 weeks of ON 01910.Na at the same dose they received during the first 24 weeks
of treatment(800 or 1500 mg/m2/day IVCI for 5 days Q2W).
Inclusion Criteria:
- Diagnosis of MDS confirmed within 4 weeks prior to study entry according to the World
Health Organization (WHO) Criteria or the French-American-British (FAB)
Classification.
- IPSS score of at least 0.5 (Intermediate-1, Intermediate-2 or High Risk MDS)
- Failure of, or insufficient response to 5-azacitidine or decitabine administered for
4 to 6 cycles.
- Failed to respond to, relapsed following, or opted not to participate in bone marrow
transplantation.
- Off all other treatments for MDS, including filgrastim (G-CSF) and erythropoietin for
at least 2 weeks, and off standard or investigational MDS therapies for four weeks.
- ECOG Performance Status 0, 1 or 2.
- 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 patients 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:
- Anemia due to factors other than MDS (including hemolysis or gastrointestinal
bleeding).
- Hypoplastic MDS (cellularity <10%).
- 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, ALT or AST
≥ 2 X ULN.
- Serum creatinine ≥ 1.5 mg/dL or calculated creatinine clearance ≤ 60 ml/min/1.73 m2
- Ascites requiring active medical management including paracentesis, or hyponatremia
(defined as serum sodium value of <134 Meq/L).
- Female 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.
- Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na
treatment start.
- Uncontrolled hypertension (defined as a systolic pressure ≥ 160 and/or a diastolic
pressure ≥ 110).
- New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly
controlled seizures.
- Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.
- Treatment with myeloid growth factors or erythropoiesis stimulating agents (ESA)
within 2 weeks of starting ON 01910.Na.
- Treatment with standard MDS therapies or investigational therapy within 4 weeks of
starting ON 01910.Na.
- Psychiatric illness/social situations that would limit the patient's ability to
tolerate and/or comply with study requirements.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (in Phase 1)
Outcome Time Frame:
1 month
Safety Issue:
Yes
Principal Investigator
Virginia Klimek, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
Onconova 04-11
NCT ID:
NCT00867061
Start Date:
March 2009
Completion Date:
September 2010
Related Keywords:
- Myelodysplastic Syndrome
- Myelodysplastic
- IPSS Intermediate 1
- IPSS Intermediate 2
- IPSS High risk
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
