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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT01167166
First received: July 19, 2010
Last updated: November 13, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Acute Myelocytic Leukemia
Acute Lymphocytic Leukemia
Myeloproliferative Disease
Chronic Myeloid Leukemia
Drug: rigosertib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Onconova Therapeutics, Inc.:

Primary Outcome Measures:
  • Dose Limiting Toxicity (DLT) [ Time Frame: Up to 8 months ] [ Designated as safety issue: Yes ]

    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

  • Change in bone marrow blast cell and peripheral blood counts at 5, 13 and 25 weeks [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Concentration of ON 01910.Na in plasma [ Time Frame: Week 1 and Week 3 ] [ Designated as safety issue: No ]
    Blood samples to determine concentration of rigosertib in plasma will be collected at 6 hours after the start of the second 24-hour infusion (Day 2) at Weeks 1 and 3.


Enrollment: 30
Study Start Date: July 2010
Study Completion Date: June 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rigosertib
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
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.
Other Name: rigosertib sodium

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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.
  3. 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.
  4. 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.
  5. ECOG Performance Status 0, 1 or 2.
  6. Willing to adhere to the prohibitions and restrictions specified in this protocol.
  7. 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.

Exclusion Criteria:

  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 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.
  10. Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start.
  11. Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160 and/or a diastolic pressure equal to or greater than 100).
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01167166

Locations
United States, Texas
University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Onconova Therapeutics, Inc.
Investigators
Principal Investigator: Jorge Cortes, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Onconova Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01167166     History of Changes
Other Study ID Numbers: 04-19
Study First Received: July 19, 2010
Last Updated: November 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Onconova Therapeutics, Inc.:
Acute Myelocytic Leukemia
Acute Lymphocytic Leukemia
Myeloproliferative Disease
Myelofibrosis
Essential thrombocythemia
Polycythemia vera
Chronic Myeloid Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myeloproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 25, 2014