Myelodysplastic Syndromes Clinical Trial
Official title:
Phase I Dose Escalation Study of ON 01910.Na With Increasing Duration of an Initial 3-Day Continuous Infusion in Patients With Refractory Leukemia or MDS
This is an open-label, Phase I study to determine the highest amount of the study drug, ON 01910.Na, that can be safety given to patients with high risk myelodysplastic syndromes (MDS) or refractory leukemias. Patients will receive ON 01910.Na (at a starting dose of 650 mg/m2) intravenously by 3-day continuous infusion once every 2 weeks. Successive courses will use longer infusion times and/or higher doses of the drug until toxicity, effectiveness, or ineffectiveness is recognized. In addition, the amount of drug in the blood will be measured, any antitumor activity will be documented, and the biological effect of ON 01910.Na on cell-cycle pathways will be evaluated in peripheral blood mononuclear cells.
Patients must have histologically documented or cytologically confirmed diagnosis of acute
myelocytic leukemia refractory to standard induction treatment, or relapsed after standard
therapy; acute lymphocytic leukemia refractory to induction treatment, or relapsed after
effective therapy; chronic myelocytic leukemia refractory to imatinib therapy or second line
tyrosine kinase inhibition, or relapsed after tyrosine kinase inhibition, in chronic,
accelerated, or blastic phase; chronic lymphocytic leukemia refractory to standard therapy,
or relapsed in second relapse; a myelodysplastic syndrome (including chronic myelomonocytic
leukemia) refractory to azacitidine; and an int-2 or high myelodysplastic syndrome relapsed
after a hypomethylating agent. Patients may not be eligible for, or must have declined, bone
marrow transplantation or other chemotherapeutic regimens known to produce consistent
remissions. Because hematopoietic criteria in leukemia and lymphoma are confounded by the
nature of the diseases themselves, there are no hematologic exclusions from treatment. If
leukopenia is clinically determined to be attributable to prior treatment, ON 01910.Na
treatment may start when the leukocyte count increases on two successive determinations
performed at least three days apart. Thrombocytopenia is not a criterion, and patients will
be supported with platelet transfusions as clinically necessary. In the absence of
leukopenia, a failed prior treatment may be succeeded immediately by entry into study of ON
01910.Na if the leukocyte count is stable or rising, on two successive determinations
performed at least three days apart, in the absence of other drug toxicity.
The patient population will involve approximately 12 to 28 patients ≥ 18 years of age in the
dose escalation portion of the protocol. All patients must have relapsed or refractory
leukemia or poor risk MDS (i.e., int-2 or high risk MDS who have failed standard therapy).
They must not be candidates for known regimens or protocol treatments of higher efficacy or
priority. Patients with relapsed/refractory leukemia or poor risk MDS must have an ECOG
Performance Status of 0, 1, or 2. Patients must have an expected survival, in the opinion of
the Investigator, to allow a sufficient observation period for evaluating ON 01910.Na, and
meet the eligibility criteria for patients with leukemia or poor risk MDS. After the
maximally tolerated dose and the Recommended Phase II Dose (RPTD) and duration are
determined, up to 12 additional patients with histologically documented or cytologically
confirmed leukemia or poor risk MDS will be added to confirm the appropriateness of the RPTD.
Inclusion criteria for the dose confirmation phase will be similar to those of the dose
escalation phase of the study, but the ECOG Performance Status must be 0 or 1.
Safety data, including laboratory parameters and adverse events, will be collected for all
patients in order to determine the qualitative and quantitative toxicity, and reversibility
of toxicity, of ON 01910.Na. Leukemic cells and MDS cells in peripheral blood will be
measured on a daily basis during infusion, and at least two times weekly during the following
week. If leukemic cells disappear from the blood or blood counts improve as defined by IWG
criteria in MDS patients, a bone marrow aspiration will be performed to determine response
status in the bone marrow.
All patients may continue therapy for at least six cycles unless rapid disease progression is
documented. Patients with an objective clinical response or stable disease can continue up to
six more cycles. Further continuation will be determined by the clinical judgment of the
Investigator.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Terminated |
NCT04313881 -
Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
|
Phase 3 | |
Recruiting |
NCT05088356 -
Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft
|
Phase 1 | |
Recruiting |
NCT04003220 -
Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
|
||
Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
Active, not recruiting |
NCT03755414 -
Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation
|
Phase 1 | |
Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
Terminated |
NCT04866056 -
Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF.
|
Phase 1/Phase 2 | |
Recruiting |
NCT04701229 -
Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
|
||
Suspended |
NCT04485065 -
Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS
|
Phase 1 | |
Recruiting |
NCT04174547 -
An European Platform for Translational Research in Myelodysplastic Syndromes
|
||
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Completed |
NCT02508870 -
A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes
|
Phase 1 | |
Completed |
NCT04543305 -
A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
|
Phase 1 | |
Recruiting |
NCT05384691 -
Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions
|
Phase 2 | |
Recruiting |
NCT05365035 -
A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
|
Phase 2 | |
Recruiting |
NCT06008405 -
Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy
|
Phase 1 | |
Not yet recruiting |
NCT05969821 -
Clonal Hematopoiesis of Immunological Significance
|
||
Withdrawn |
NCT05170828 -
Cryopreserved MMUD BM With PTCy for Hematologic Malignancies
|
Phase 1 |