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A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination With Cytarabine in Pediatric Patients With Refractory/Relapsed Leukemia

Phase 1/Phase 2
1 Year
30 Years
Not Enrolling

Thank you

Trial Information

A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination With Cytarabine in Pediatric Patients With Refractory/Relapsed Leukemia



- To define the overall response rate (complete remission or remission without platelet
recovery) in young patients with relapsed or refractory acute myeloid leukemia (AML) or
acute lymphoblastic leukemia (ALL) treated with clofarabine in combination with


- To determine the safety profile and tolerability of clofarabine when given in
combination with cytarabine in patients with and without prior stem cell

- To identify apoptosis specific genes that are important in mediating response to
clofarabine and cytarabine.

- To quantitate the level of human equilibrative nucleoside transporter proteins (hENT1
and hENT2) and human concentrative nucleoside transporter proteins (hCNT2 and hCNT3) in
blasts of these patients.

- To determine gene expression profiles at study entry and at time of relapse in order to
isolate profiles that may predict response and also to complement apoptosis specific
protein arrays.

- To perform serial measurements of minimal residual disease (MRD) to provide an
objective determination of the effectiveness of this treatment regimen and to correlate
with post remission events (relapse, death).

- To perform FLT3/ITD analysis to help determine the prevalence and clinical significance
of this somatic mutation in patients with relapsed AML.

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]). (Phase I closed to accrual as of 09/16/09)

- Intrathecal CNS prophylaxis (all patients with ALL and at physician's discretion for
patients with AML or acute leukemia of ambiguous lineage): Patients receive intrathecal
(IT) cytarabine on day 0 of the first course of induction therapy. Patients also
receive IT methotrexate on day 1 of the second course of induction therapy and on day 1
of all courses of maintenance therapy.

- Induction therapy:

- Course 1: Patients receive cytarabine IV over 2 hours and clofarabine IV over 2
hours on days 1-5. 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 followed by cytarabine IV
over 2 hours on days 1-5. After the second course of induction therapy, patients
with M2 or M3 bone marrow at days 14-21 are removed from the study. Patients with
M1 bone marrow proceed to maintenance therapy 14-42 days after the initiation of
course 2.

- Maintenance therapy: Patients receive clofarabine and cytarabine as in induction
therapy. Treatment repeats every 14-42 days for up to 10 courses in the absence of
disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection periodically for correlative
laboratory studies.

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

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

Inclusion Criteria


- Histologically confirmed diagnosis of 1 of the following:

- Acute myeloid leukemia (AML) with ≥ 5% blasts in the bone marrow (M2/M3 bone
marrow) with or without extramedullary disease

- Acute lymphoblastic leukemia (ALL) with > 25% blasts in the bone marrow (M3 bone
marrow) with or without extramedullary disease

- Acute leukemia of ambiguous lineage with ≥ 5% blasts in the bone marrow (M2/M3
bone marrow) with or without extramedullary disease

- Disease must have relapsed after or be refractory to prior induction therapy

- Patients with AML or acute leukemia of ambiguous lineage must be in first
relapse OR refractory to first induction therapy with ≤ 1 attempt at remission

- Patients with AML who enroll on the phase I portion of the study must have
received prior mitoxantrone hydrochloride and cytarabine for newly
diagnosed AML (phase I closed to accrual as of 09/16/09)

- Patients with ALL must be in second or third relapse (≤ 3 prior induction
regimens) OR refractory to reinduction in first relapse

- Patients with ALL refractory to first induction therapy are not eligible

- No acute promyelocytic leukemia

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


- 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

- Direct bilirubin ≤ 1.5 times upper limit of normal (ULN)

- 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 during and for ≥ 3 months after
completion of study treatment

- No known hepatitis B or C infection or history of cirrhosis


- See Disease Characteristics

- Recovered from all prior therapy*

- At least 14 days since prior cytotoxic therapy (except hydroxyurea and intrathecal

- 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: *Patients who relapse during ALL
maintenance therapy do not require a waiting period.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of clofarabine in combination with cytarabine (Phase I closed to accrual as of 09/16/09)

Safety Issue:


Principal Investigator

Bassem I. Razzouk, MD

Investigator Role:

Study Chair

Investigator Affiliation:

St. Vincent Indianapolis Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • acute undifferentiated leukemia
  • adult acute minimally differentiated myeloid leukemia (M0)
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloblastic leukemia without maturation (M1)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • childhood acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • childhood acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • childhood acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • childhood acute erythroleukemia (M6)
  • adult acute megakaryoblastic leukemia (M7)
  • childhood acute megakaryocytic leukemia (M7)
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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Mayo Clinic Cancer Center Rochester, Minnesota  55905
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
Newark Beth Israel Medical Center Newark, New Jersey  07112
UMASS Memorial Cancer Center - University Campus Worcester, Massachusetts  01605-2982
Ellis Fischel Cancer Center at University of Missouri - Columbia Columbia, Missouri  65203
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Children's Hospital of Orange County Orange, California  92668
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Mercy Hospital Kansas City, Missouri  64108
St. Joseph's Hospital and Medical Center Paterson, New Jersey  07503
Children's Hospital and Regional Medical Center - Seattle Seattle, Washington  98105
Nemours Children's Clinic Jacksonville, Florida  32207
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Driscoll Children's Hospital Corpus Christi, Texas  78466
Cook Children's Medical Center - Fort Worth Fort Worth, Texas  76104
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Palmetto Health South Carolina Cancer Center Columbia, South Carolina  29203
Children's Hospital of the King's Daughters Norfolk, Virginia  23507
Midwest Children's Cancer Center at Children's Hospital of Wisconsin Milwaukee, Wisconsin  53226
Blumenthal Cancer Center at Carolinas Medical Center Charlotte, North Carolina  28232-2861
Overlook Hospital Summit, New Jersey  07902-0220
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital Long Beach, California  90801
Lee Cancer Care of Lee Memorial Health System Fort Myers, Florida  33901
Nemours Children's Clinic - Orlando Orlando, Florida  32806
St. Joseph's Cancer Institute at St. Joseph's Hospital Tampa, Florida  33607
St. Vincent Indianapolis Hospital Indianapolis, Indiana  46260
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore, Maryland  21215
Hackensack University Medical Center Cancer Center Hackensack, New Jersey  07601
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Presbyterian Cancer Center at Presbyterian Hospital Charlotte, North Carolina  28233-3549
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Rainbow Babies and Children's Hospital Cleveland, Ohio  44106-5000
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Baylor University Medical Center - Houston Houston, Texas  77030-2399
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Providence Cancer Center at Sacred Heart Medical Center Spokane, Washington  99220-2555
James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York  14642
Rady Children's Hospital - San Diego San Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Alfred I. duPont Hospital for Children Wilmington, Delaware  19803
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Washington, District of Columbia  20007
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus Atlanta, Georgia  30322
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center Savannah, Georgia  31403-3089
University of Illinois Cancer Center Chicago, Illinois  60612-7243
Simmons Cooper Cancer Institute Springfield, Illinois  62794-9677
Indiana University Melvin and Bren Simon Cancer Center Indianapolis, Indiana  46202-5289
Tulane Cancer Center Office of Clinical Research Alexandria, Louisiana  71315-3198
CancerCare of Maine at Eastern Maine Medical Center Bangor, Maine  04401
C.S. Mott Children's Hospital at University of Michigan Medical Center Ann Arbor, Michigan  48109-0286
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
University of Mississippi Cancer Clinic Jackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
CCOP - Nevada Cancer Research Foundation Las Vegas, Nevada  89109-2306
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School New Brunswick, New Jersey  08903
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center New York, New York  10032
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Dayton Children's - Dayton Dayton, Ohio  45404-1815
Legacy Emanuel Hospital and Health Center and Children's Hospital Portland, Oregon  97227
Penn State Children's Hospital Hershey, Pennsylvania  17033-0850
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Carilion Medical Center for Children at Roanoke Community Hospital Roanoke, Virginia  24014
UAB Comprehensive Cancer Center Birmingham, Alabama  35294
Greenville Hospital Cancer Center Greenville, South Carolina  29605
Children's Hospital Colorado Center for Cancer and Blood Disorders Aurora, Colorado  80045
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503