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

NCT01701375 | Terminated Phase 1 Results DMC

• 2 other identifiers: J1275NA_00076003
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• 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

  42 days

Secondary Outcomes (1)

• To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone

  42 days

Study Arms (1)

Arm 1

EXPERIMENTAL

* 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

Drug: PD 0332991

Interventions

PD 0332991 DRUG

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

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• The Leukemia and Lymphoma Society: collaborator
• Pfizer: collaborator

Study Sites (2)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

palbociclib

Results Point of Contact

• Title: Ivana Gojo, MD
• Organization: Johns Hopkins University

Igojo1@jhmi.edu

410-502-7726

Study Officials

• Judith Karp, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: October 5, 2012
• Study Start: September 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 9, 2013
• Results First Posted: September 9, 2013

Record last verified: 2013-08

Locations

US (2)