Back to resultsA 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
Primary Purpose
Relapsed Acute Leukemia, Refractory Acute Leukemia, High-Risk Myelodysplasia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PD 0332991
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Acute Leukemia
Eligibility Criteria
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
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Weill Cornell Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1
Arm Description
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
Outcomes
Primary Outcome Measures
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
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
Secondary Outcome Measures
To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone
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
Full Information
NCT ID
NCT01701375
First Posted
September 11, 2012
Last Updated
August 30, 2013
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
The Leukemia and Lymphoma Society, Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01701375
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2013
Overall Recruitment Status
Terminated
Why Stopped
Material sponsor withdrew support
Study Start Date
September 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
The Leukemia and Lymphoma Society, Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Acute Leukemia, Refractory Acute Leukemia, High-Risk Myelodysplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
PD 0332991
Intervention Description
• PD 0332991 will be given orally days 1,2,3
Primary Outcome Measure Information:
Title
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
Description
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
Time Frame
42 days
Secondary Outcome Measure Information:
Title
To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone
Description
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
Time Frame
42 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Karp, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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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