Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active 1 to 30 NCI COG-AAML0523 AAML0523, NCT00372619

Objectives

Primary

1. Define the overall response rate (complete remission or remission without platelet recovery) in pediatric patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) treated with clofarabine in combination with cytarabine.

Secondary

1. Determine the safety profile and tolerability of clofarabine when given in combination with cytarabine in patients with and without prior stem cell transplantation.

Entry Criteria

Disease Characteristics:

• Histologically confirmed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL)
  • More than 25% blasts in the bone marrow (M3 bone marrow) (ALL)
  • At least 5% bone marrow blasts in the bone marrow (M2/M3 bone marrow) with or without extramedullary disease (AML)



• Disease must have relapsed after or be refractory to prior induction therapy
  • AML patients must be in first relapse OR refractory to induction therapy with ≤ 1 attempt at remission induction
    • Must have received prior mitoxantrone hydrochloride and cytarabine for newly diagnosed AML (phase I)
  • ALL patients must be in second or third relapse (no more than 3 prior induction regimens) OR refractory to reinduction in first relapse
    • ALL refractory to first induction therapy is not eligible



• No CNS 3 involvement (i.e., WBC ≥ 5/μL in the cerebrospinal fluid with blasts present on cytospin)

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from all prior therapy*
• At least 14 days since prior cytotoxic therapy (48 hours since prior hydroxyurea to decrease WBC)*
• At least 7 days since prior biologic agent*
• At least 14 days since prior monoclonal antibody therapy*
• No more than 1 prior autologous or allogeneic hematopoietic stem cell transplantation
  • No evidence of active graft-vs-host disease
  • At least 4 months since transplantation
• No other concurrent chemotherapy or immunomodulating agents
• No other concurrent investigational therapy

 [Note: *Relapse during maintenance therapy does not require a waiting period (ALL)]

Patient Characteristics:

• Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age) OR ECOG PS 0-2
• Life expectancy ≥ 8 weeks
• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (conjugated serum bilirubin < ULN if total bilirubin is elevated)
• ALT < 2.5 times ULN (unless it is related to leukemic involvement)
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 45% by gated radionuclide study
• No evidence of dyspnea at rest or exercise intolerance
• Pulse oximetry > 94% at room air
• Amylase ≤ 1.5 times ULN
• Lipase < 1.5 times ULN
• No active, uncontrolled grade 3 or 4 infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known hepatitis B or C infection or history of cirrhosis

Expected Enrollment

A total of 87 patients will be accrued for this study.

Outcomes

Maximum tolerated dose of clofarabine in combination with cytarabine
Overall response rate

Safety and tolerability as measured by CTCAE v3.0

Outline

This is a multicenter, phase I, dose-escalation study of clofarabine followed by a phase II study. Patients are stratified according to disease (acute lymphoblastic leukemia [ALL] vs acute myeloid leukemia [AML]).

• Intrathecal CNS prophylaxis (all patients with ALL and at physicians discretion for patients with AML): Patients receive intrathecal (IT) cytarabine on day 0 of the first course of induction therapy and IT methotrexate on day 1 of the second course of induction therapy.



• Induction therapy:
  • Course 1: Patients receive cytarabine IV over 2 hours on days 1-5 and clofarabine IV over 2 hours on days 2-6. Patients with ≥ 5% blasts (i.e., M2 or M3 bone marrow) at days 14-21 proceed immediately to course 2 of induction therapy. Patients with < 5% blasts (i.e., M1 bone marrow) may proceed to course 2 of induction therapy at blood count recovery or at day 42.
  
  
  
  • Course 2: Patients receive clofarabine IV over 2 hours (at the same dose as in course 1) followed by cytarabine IV over 2 hours on days 1-5.
  
  
  

  During the first course of induction therapy, cohorts of 10 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 10 patients experience dose-limiting toxicity.

  After the second course of induction therapy, patients with M2 or M3 bone marrow are removed from the study. Patients with M1 bone marrow proceed to maintenance therapy 14-42 days after day 1 of course 2 of induction therapy.




• Maintenance therapy: Patients receive IT methotrexate on day 0. Patients also receive clofarabine at the MTD and cytarabine as in course 2 of induction therapy. Treatment repeats every 14-42 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 5 years.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Bassem Razzouk, MD, Protocol chair		Ph: 317-338-4673 Email: bassem.razzouk@stjude.org
Todd Cooper, DO, Protocol co-chair		Ph: 205-939-9285 ext. 5855

U.S.A.
Alabama
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
California
	Orange
	Children's Hospital of Orange County
		Violet Shen	Ph:  714-532-8636
District of Columbia
	Washington
	Children's National Medical Center
		Clinical Trials Office - Children's National Medical Center	Ph:  202-884-2549
Illinois
	Chicago
	Children's Memorial Hospital - Chicago
		David Walterhouse	Ph:  773-755-6514
Indiana
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Ph:  410-955-8804
			Email: jhcccro@jhmi.edu
Michigan
	Ann Arbor
	C.S. Mott Children's Hospital at University of Michigan Medical Center
		Clinical Trials Office - C.S. Mott Children's Hospital	Ph:  1-800-865-1125
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620
Mississippi
	Jackson
	University of Mississippi Cancer Clinic
		Gail Megason	Ph:  601-984-5220
Missouri
	St. Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Robert Hayashi	Ph:  314-454-4118
New York
	New York
	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
		Clinical Trials Office - Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Ph:  212-305-8615
Ohio
	Cincinnati
	Cincinnati Children's Hospital Medical Center
		Clinical Trials Office - Cincinnati Children's Hospital Medical Center	Ph:  513-636-0161
Pennsylvania
	Philadelphia
	Children's Hospital of Philadelphia
		Peter Adamson	Ph:  215-590-6359
	Pittsburgh
	Children's Hospital of Pittsburgh
		Clinical Trials Office - Children's Hospital of Pittsburgh	Ph:  412-692-5573
Tennessee
	Memphis
	St. Jude Children's Research Hospital
		Clinical Trials Office - St. Jude Children's Research Hospital	Ph:  901-495-4644
	Nashville
	Vanderbilt-Ingram Cancer Center
		Clinical Trials Office - Vanderbilt-Ingram Cancer Center	Ph:  1-800-811-8480;
Texas
	Dallas
	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
		Clinical Trials Office - Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Ph:  866-460-4673; 214-648-7097
	Houston
	Baylor University Medical Center - Houston
		Alberto Pappo	Ph:  832-822-4248
Washington
	Seattle
	Children's Hospital and Regional Medical Center - Seattle
		Douglas Hawkins	Ph:  206-987-3096
Canada
Ontario
	Toronto
	Hospital for Sick Children
		Ronald Grant	Ph:  416-813-8885
Quebec
	Montreal
	Hopital Sainte Justine
		Yvan Samson	Ph:  514-345-4969

Registry Information
Official Title		A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination with Cytarabine in Pediatric Patients with Refractory/Relapsed Leukemia
Trial Start Date		2007-03-12
Trial Completion Date		2010-11-19 (estimated)
Registered in ClinicalTrials.gov		NCT00372619
Date Submitted to PDQ		2006-06-30
Information Last Verified		2008-12-24
NCI Grant/Contract Number		CA98543

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