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 has been terminated.
(Material sponsor withdrew support)
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: August 30, 2013
Last verified: August 2013

September 11, 2012
August 30, 2013
September 2012
April 2013   (final data collection date for primary outcome measure)
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone. [ Time Frame: 42 days ] [ Designated as safety issue: Yes ]
The number of participants experiencing 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
  • 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.
Complete list of historical versions of study NCT01701375 on ClinicalTrials.gov Archive Site
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
Not Provided
Not Provided
Not Provided
 
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

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
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Relapsed Acute Leukemia
  • Refractory Acute Leukemia
  • High-Risk Myelodysplasia
Drug: PD 0332991
• PD 0332991 will be given orally days 1,2,3
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
April 2013
April 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01701375
J1275, NA_00076003
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
  • The Leukemia and Lymphoma Society
  • Pfizer
Study Chair: Judith Karp, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
August 2013

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