Safety and Efficacy of 72-hour and 120-hour Infusion of Rigosertib in Acute Myeloid Leukemia (AML) and Acute Lymphoid Leukemia (ALL)

NCT01167166 | Completed Phase 1

• 1 other identifier: 04-19
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

For patients with leukemia who have not responded to or have progressed after an initial response to standard therapy, therapeutic options are limited. Although responses to standard regimens do occur, durable remissions are achieved infrequently and current regimens are not curative in the majority of patients. Identification of active agents in patients with relapsed Acute Myeloid Leukemia (AML) ultimately affords the potential for use upfront as a component of induction regimens that may translate to improved outcome. Therefore, development of new agents is of critical importance. This study will look at a new, investigational agent, ON 01910.Na, to determine if it has the potential to help Patients with AML and Acute Lymphocytic Leukemia (ALL) and transformed Myeloproliferative Neoplasms.

Conditions

Acute Myelocytic Leukemia; Acute Lymphocytic Leukemia; Myeloproliferative Disease; Chronic Myeloid Leukemia

Keywords

Acute Myelocytic Leukemia; Acute Lymphocytic Leukemia; Myeloproliferative Disease; Myelofibrosis; Essential thrombocythemia; Polycythemia vera; Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  DLT: adverse event possibly related that is: * Grade ≥ 3 non-hematological toxicity other than nausea, vomiting, diarrhea, fever, esophagitis/dysphagia * Grade ≥ 3 nausea and vomiting uncontrolled by antiemetics; grade ≥ 3 diarrhea uncontrolled by antidiarrheal agents; grade ≥ 3 drug-induced fever uncontrolled by antipyretics; grade ≥3 metabolic abnormalities that are not controlled by optimal supportive care measures * Grade ≥ 3 stomatitis and/or esophagitis/dysphagia lasting \> 3 days * Marrow cellularity \<5% on day 42 or later (6 weeks) from start of therapy without evidence of leukemia

  Up to 8 months

• Change in bone marrow blast cell and peripheral blood counts at 5, 13 and 25 weeks

  Determine the clinical response rate (complete or partial remission) according to response criteria in patients with relapsed/refractory acute myeloid or lymphocytic leukemia (1 Cheson BD, Bennett JM, Kopecky KJ, et al. Revised Recommendations of the International Working Group for Diagnosis, Standardization or Response Criteria, Treatment Outcomes and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. JCO 21:4642, 2003).

  18 months

Secondary Outcomes (1)

• Concentration of ON 01910.Na in plasma

  Week 1 and Week 3

Study Arms (1)

rigosertib

EXPERIMENTAL

Patients will receive 2400 mg dose of rigosertib as a intravenous continuous infusion over 24 hours for 72 to 120 consecutive hours every 2 weeks for the first 4 weeks then will receive oral rigosertib at a 560 mg twice-daily dose as capsules taken continuously.

Drug: rigosertib

Interventions

rigosertib DRUG

The dose of rigosertib will be 2400 mg/24h as an intravenous continuous infusion over 72 or 120 hours every 2 weeks for 2 cycles then as oral capsules administered at a dose of 560 mg twice daily on a continuous basis.

Also known as: rigosertib sodium

rigosertib

Eligibility Criteria

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

You may qualify if:

• 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 (including transformed myeloproliferative diseases with at least 10% blasts in bone marrow and chronic myeloid leukemia in a blast phase)
• Transformed myeloproliferative neoplasms (MPNs; i.e., 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
• Acute lymphocytic leukemia (ALL) refractory to induction treatment, or relapsed after standard therapy
• Patients should not have received any prior chemotherapy for their leukemia or transformed 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.
• 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.
• 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.
• ECOG Performance Status 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• 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.

You may not qualify if:

• Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
• Known HIV-1 seropositivity.
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
• Uncontrolled active systemic infection not adequately responding to appropriate therapy.
• Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease.
• ALT or AST ≥ 2.5 X ULN.
• Serum creatinine ≥ 2.0 mg/dL.
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 Meq/L).
• 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 before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum or urine beta-HCG pregnancy test at screening.
• Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start.
• Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160 and/or a diastolic pressure equal to or greater than 100).
• New onset seizures (within 3 months prior to the first dose of rigosertib) 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)

University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

  RESULT

Related Links

• Patient and cancer information on M. D. Anderson Cancer Center web site.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myeloproliferative Disorders; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Primary Myelofibrosis; Thrombocythemia, Essential; Polycythemia Vera

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  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: July 19, 2010
• First Posted: July 22, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2014
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

US (1)