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

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NCT01701375

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Study Location
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287, United States
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Contact
1-800-718-1021
[email protected]
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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Relapsed Acute Leukemia, Refractory Acute Leukemia, High-Risk Myelodysplasia
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- • 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

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Relapsed Acute Leukemia, Refractory Acute Leukemia, High-Risk MyelodysplasiaA 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
NCT01701375
  1. Baltimore, Maryland
  2. New York, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
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  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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 Arms  ICMJE 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 Terminated
Actual Enrollment  ICMJE
 (submitted: August 30, 2013)		2
Original Estimated Enrollment  ICMJE
 (submitted: October 3, 2012)		42
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date April 2013   (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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01701375
Other Study ID Numbers  ICMJE J1275
NA_00076003 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE
  • The Leukemia and Lymphoma Society
  • Pfizer
Investigators  ICMJE
Study Chair:Judith Karp, MDSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date August 2013

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