10147 A Phase II randomized study of topotecan/carboplatin with or without veliparib in advanced myeloproliferative disorders and chronic myelomonocytic leukemia
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
II
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Keywords
- Acute Myeloid Leukemia
- Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
- Atypical Chronic Myeloid Leukemia
- Chronic Myelomonocytic Leukemia
- Essential Thrombocythemia
- Myelodysplastic/Myeloproliferative Neoplasm
- Myelofibrosis
- Polycythemia Vera
- Recurrent Acute Myeloid Leukemia
- Refractory Acute Myeloid Leukemia
Contact Us
(410) 955-8964Brief Summary
This study has two study groups: Group 1 will get the topotecan (1.2mg/m2/day)/carboplatin chemotherapy given with the study drug veliparib. Group 2 will get topotecan(1.6mg/m2/day)/carboplatin chemotherapy.
The topotecan/carboplatin chemotherapy are given by vein (IV infusion) on days 3-7 in Group 1 and days 1-5 in Group 2. The veliparib capsules are taken twice daily on days 1-21 and must be swallowed whole. Do not break or chew the capsules.
A computer will by chance assign you to treatment groups in the study. This is called randomization. This is done by chance because no one knows if one study group is better or worse than the others. In this study 2 of every 3 participants will be assigned by chance to Group 1. You and your study doctor will be aware of the group the computer assigns you to.
You will receive the study protocol for 21 days in the hospital. After you finish, your doctor will continue to watch you for side effects and follow your condition for recovery of normal blood counts over the course of the next several weeks. When your blood counts recover, a repeat bone marrow test will be done to assess the tumor response to the study combination. One cycle of this therapy is 28 days total with a maximum of 21 days (Group 1) or 5 days (Group 2) of study drugs. If you have responded to the study combination, you are able to receive up to three additional course of the sudy combination with the next cyle starting anytime between days 28 to 63. Another option is that you may proceed to allogeneic transplantation.
Eligibility
Inclusion Criteria:
PRE-REGISTRATION ELIGIBILITY CRITERIA
Newly diagnosed acute myeloid leukemia (AML) associated with antecedent myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia and related undifferentiated myeloproliferative/myelodysplastic disorders)
Relapsed/refractory AML associated with antecedent myeloproliferative disorder (polycythemia vera, essential thrombocythemia, myelofibrosis, atypical chronic myeloid leukemia, chronic myelomonocytic leukemia and related undifferentiated myeloproliferative/myelodysplastic disorders) who have received two or fewer prior induction chemotherapy courses
Accelerated phase myeloproliferative disorders per Zeider et al with two or fewer prior therapies
- For aggressive phase myeloproliferative disorders (MPD) (polycythemia vera, essential thrombocythemia, Philadelphia [Ph]-negative chronic myelogenous leukemia), one or more of the following criteria must be met: marrow blasts > 5%, peripheral blood blasts plus progranulocytes > 10%, new onset or increasing myelofibrosis, new onset or > 25% increase in hepatomegaly or splenomegaly, new onset constitutional symptoms (fever, weight loss, splenic pain, bone pain). Zeider et al
- For chronic myelomonocytic leukemia (CMML), the following criteria must be met: 5-19% bone marrow blasts (aggressive) or >= 20% marrow blasts (transformation)
Bone marrow and/or peripheral blood specimens will be submitted for correlative studies; patients with a dry tap will still be eligible
RANDOMIZATION ELIGIBILITY CRITERIA
Bone marrow aspirate and/or peripheral blood specimens were submitted to the central lab and site has confirmation by the local institution that the patient meets one of the criteria specified above
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 or Karnofsky >= 60%
Total bilirubin less than 2.0 mg/dL unless due to Gilbert's syndrome, then less than 5.0 mg/dL
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less than 5 x institutional upper limit of normal
Creatinine clearance glomerular filtration rate (GFR) greater than 30 ml/min per modified Cockcroft-Gault formula
Interval of greater than 4 weeks since allogeneic blood or marrow transplantation (BMT) if performed; and absence of active graft versus host disease (GVHD)
The effects of veliparib on the developing human fetus are unknown; for this reason and because PARP inhibiting agents as well as topoisomerase inhibitors and platinating agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months following the last dose of study drug; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of veliparib administration
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study with the exception of hydroxyurea for cytoreduction; therapy with tyrosine kinase inhibitors (TKIs) directed against JAK2, BCR-ABL or FLT3 will be allowed to be continued until 24 hours prior to start of therapy on trial
- Patients with active uncontrolled infection; antibiotic therapy for fevers, and continuation of treatment of prior infection are allowed
- Patients who have active central nervous system (CNS) disease are excluded; patients with known active CNS leukemia should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Patients who are receiving any other investigational agents; patients who have completed therapy with an investigational agent should be off this therapy for at least 5 half-lives or two weeks, whichever is shorter
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to veliparib, topotecan or carboplatin
- Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because veliparib is PARP inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with veliparib, breastfeeding should be discontinued if the mother is treated with veliparib; these potential risks may also apply to topotecan and carboplatin used in this study
- Human immunodeficiency virus (HIV)-patients positive patients are not excluded if they have CD4+ cells >= 250/mm^3 and negligible viral load and are on a stable combination antiretroviral therapy
- History of uncontrolled seizure disorder, including focal or generalized seizure within the past year