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

NCT ID: NCT01701375

Last Updated: 2013-09-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2013-04-30

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

Conditions

Relapsed Acute Leukemia; Refractory Acute Leukemia; High-Risk Myelodysplasia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

PD 0332991

Intervention Type: DRUG

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

Interventions

PD 0332991

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Karp, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Weill Cornell Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

NA_00076003

Identifier Type: OTHER

Identifier Source: secondary_id

J1275

Identifier Type: -

Identifier Source: org_study_id