A Phase 1/2, Single Arm Study to Assess the Efficacy and Safety of Rigosertib (ON 01910.Na) Administered as 72-Hour and 120-Hour Continuous Intravenous Infusions Every Other Week for Two Cycles Then as Twice-daily Oral Capsules Given Continuously in Patients with Relapsed/Refractory Acute Myeloid or Lymphocytic Leukemia or Transformed Myeloproliferative Neoplasms
The goal of the Phase I portion of this clinical research study is to check the safety of a drug called Rigosertib (ON 01910.Na) when given to patients with AML, ALL, or an MPN. The goal of the Phase II portion of this study is to learn if rigosertib can help to control the disease in patients with AML, ALL, or an MPN. The safety of this drug will continue to be studied.
Disease Group: Leukemia
Treatment Agent: ON 01910.Na
Treatment Location: Only at MD Anderson
Sponsor: Onconova Therapeutics Inc.
Primary Objectives: Phase 1: Define the hematologic and non-hematologic toxicities of rigosertib (ON 01910.Na) administered as 3- and 5-day continuous intravenous infusions every 2 weeks at a dose of 2400 mg/day for 2 cycles, then as oral capsules administered at a dose of 560 mg twice daily on a continuous basis, and define the MTD of rigosertib. Phase 2: Determine the clinical response rate (complete or partial remission) according to response criteria in patients with relapsed/refractory acute myeloid or lymphocytic leukemia or transformed myeloproliferative neoplasms. Secondary Objectives: The secondary objectives are to assess: Time and duration of response Time to progression Overall survival at 24 weeks
IRB Review and Approval Date: 08/24/2010
Recruitment Status: Not Accepting
Projected Accrual: N/A
1) >/= 18 years of age.
2) Histologically documented or cytologically confirmed diagnosis of one of the following hematological malignancies: Acute myelocytic leukemia (AML) refractory to standard induction treatment, or relapsed after standard therapy; Transformed myeloproliferative neoplasms (myelofibrosis, essential thrombocythemia [ET], polycythemia vera [PV] with at least 10% blasts in bone marrow and chronic myeloid leukemia in a blast phase) refractory or relapsing after standard therapy; or Acute lymphocytic leukemia (ALL) refractory to induction treatment, or relapsed after standard therapy.
3) Patients should not have received any prior chemotherapy for their leukemia or transformed myeloproliferative neoplasm (MPN) within 14 days and should have recovered from any toxicity related to prior chemotherapy to at least grade 1. In the presence of rapidly proliferating disease, patients can be included after a washout period of 7 days. Hydroxyurea can be administered as clinically indicated, and no washout is required.
4) Patients may not be candidates for, or must have declined, bone marrow transplantation from an HLA-identical donor in the immediate future (ie, within 4 weeks) or other chemotherapeutic regimens known to produce consistent remissions.
5) Patients with known meningeal infiltration may be enrolled only if radiation has been completed, and a clearing of peripheral blood blasts has been noted. Intrathecal therapy can be continued if judged to be in the best interest of the patient to prevent recurrence, provided there is no toxicity associated with it and there has been clearance of blasts in the cerebrospinal fluid.
6) ECOG Performance Status 0, 1 or 2.
7) Willing to adhere to the prohibitions and restrictions specified in this protocol.
8) Patient 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.
1) Any active malignancy within the past year except basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix or breast.
2) Known HIV-1 seropositivity.
3) Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
4) Uncontrolled active systemic infection not adequately responding to appropriate therapy.
5) Total bilirubin >/= 1.5 mg/dL not related to hemolysis or Gilbert’s disease.
6) ALT or AST >/= 2.5 X ULN.
7) Serum creatinine >/= 2.0 mg/dL.
8) Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 Meq/L).
9) Female patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements (condom use). Patients of reproductive potential who do not agree to use 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; Female patients with reproductive potential who do not have a negative serum or urine betaHCG pregnancy test at screening.
10) Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start.
11) Uncontrolled hypertension (defined as a systolic pressure >/= 160 and/or a diastolic pressure >/= 110).
12) New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures.
13) Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.
14) Psychiatric illness/social situations that would limit the patient’s ability to tolerate and/or comply with study requirements.
Information and next steps
Phase I/Phase II
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