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TERMINATEDPHASE1

A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia

A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias

NCT01701375•Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

View on ClinicalTrials.gov

Summary

1.1 Primary Objectives * To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory disease * To determine the direct cytotoxic effects of single agent PD 0332991 on malignant blasts * To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone * To determine if the timed sequential combination of PD 0332991 with ara-C and mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS 1.2 Secondary Objectives: * To determine the ability of PD 0332991 to directly induce apoptosis in malignant cell populations in vivo * To obtain pharmacodynamic (PD) data regarding the ability of PD 0332991 to arrest malignant cells in the G 1 phase of cell cycle, followed by synchronized release of those cells into S phase upon discontinuation of PD 0332991 and resultant enhanced ara-C cytotoxicity

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Adults age ≥ 18 years
•* Multilineage bone marrow failure
•* Serum creatinine ≤ 2.0 mg/dl
•* Hepatic enzymes (AST, ALT) ≤ 3x upper limit of normal (ULN)
•* Bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's disease, hemolysis or leukemic infiltration
•* Left ventricular ejection fraction ≥ 45%
•* QTc ≤ 470 msec
•* RB expression is required for the action of PD 0332991. Because rb deletions and mutations are rare in acute leukemias and MDS, screening for RB expression will not be required before enrollment. Pretreatment biopsies will be stored and analyzed for RB expression if needed subsequently.

Exclusion Criteria

•• No more than 5 cytotoxic regimens
•* Previous allogeneic or autologous stem cell transplantation permitted
•* ≥ 3 weeks delay from prior cytotoxic chemotherapy or radiation therapy
•* ≥ 2 week delay from prior biologic therapies including hematopoietic growth factors and vidaza or decitabine
•* If using Hydroxyurea, steroids, tyrosine kinase/src kinase inhibitors, arsenic, interferon for count control, must be off therapy for ≥ 48 hours prior to beginning PD 0332991
•* No concomitant use of potent CYP450 3A4 inhibitors (e.g. triazole antifungal agents) or inducers (e.g. omperazole, dilantin, dexamethasone) within 7 days prior to beginning PD 0332991

Locations (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Weill Cornell Medical Center

New York, New York, United States

Key Dates

Start Date

September 1, 2012

Primary Completion Date

April 1, 2013

Completion Date

April 1, 2013

Last Updated

September 9, 2013

Enrollment

ACTUAL participants

Conditions

Relapsed Acute LeukemiaRefractory Acute LeukemiaHigh-Risk Myelodysplasia

Interventions

PD 0332991

DRUG

Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

NCT04898894

Acute Leukemia of Ambiguous Lineage in RelapseAcute Myeloid Leukemia, in Relapse+2 more

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WITHDRAWNPHASE1

A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias

NCT06474663

Refractory Acute LeukemiaRelapsed Acute Leukemia

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 9, 2013Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Phase 1 Trial of TST of PD 0332991 Followed by Cytarabine and Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasia

Inclusion Criteria

Exclusion Criteria

Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias

Venetoclax and Quizartinib in Treating Patients With FLT3-mutated Recurrent or Refractory Acute Myeloid Leukemia

High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

Study Evaluating Safety and Efficacy of CAR-T Cells Targeting CD123 in Patients With Acute Leukemia