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

This study is currently recruiting participants.

Verified January 2013 by Sidney Kimmel Comprehensive Cancer Center

Sponsor:

Collaborators:

The Leukemia and Lymphoma Society

Pfizer

Information provided by (Responsible Party):

Sidney Kimmel Comprehensive Cancer Center

ClinicalTrials.gov Identifier:

NCT01701375

First received: September 11, 2012

Last updated: January 14, 2013

Last verified: January 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

September 11, 2012

Last Updated Date

January 14, 2013

Start Date ^ICMJE

September 2012

Estimated Primary Completion Date

September 2014 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

To determine the tolerability and toxicities of the combination. [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

The toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Original Primary Outcome Measures ^ICMJE

To determine the tolerability and toxicities of the combination. [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
The toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be reported.
• To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
The toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be reported.

Change History

Complete list of historical versions of study NCT01701375 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]

Dose escalation decisions will be based on nonhematologic toxicities in Cycle 1 (28 days) and hematologic toxicities, in the case of an aplastic marrow through Day 56, For cytopenias including ANC < 500/mm3 or platelets < 50, 000/mm3 a bone marrow will be performed between days 42 and 49.. Dose limiting toxicity (DLT) will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief 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

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Relapsed Acute Leukemia
Refractory Acute Leukemia
High-Risk Myelodysplasia

Intervention ^ICMJE

Drug: PD 0332991

• PD 0332991 will be given orally days 1,2,3

Study Arm (s)

Experimental: Arm 1

PD 0332991 will be given orally days 1,2,3
Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6
Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose

Intervention: Drug: PD 0332991

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

September 2016

Estimated Primary Completion Date

September 2014 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Judith Karp, MD	410-502-7726	jkarp2@jhmi.edu
Contact: Jackie Greer, RN	410-614-1329	jgreer6@jhmi.edu

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT01701375

Other Study ID Numbers ^ICMJE

J1275, NA_00076003

Has Data Monitoring Committee

Yes

Responsible Party

Sidney Kimmel Comprehensive Cancer Center

Study Sponsor ^ICMJE

Sidney Kimmel Comprehensive Cancer Center

Collaborators ^ICMJE

The Leukemia and Lymphoma Society
Pfizer

Investigators ^ICMJE

Study Chair:

Judith Karp, MD

Sidney Kimmel Comprehensive Cancer Center

Information Provided By

Sidney Kimmel Comprehensive Cancer Center

Verification Date

January 2013

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

To Top