Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00372619

Purpose

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: clofarabine Drug: cytarabine Drug: methotrexate	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Study of CLOLAR® (Clofarabine, IND# 73, 789) in Combination With Cytarabine in Pediatric Patients With Refractory/Relapsed Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Methotrexate Cytarabine hydrochloride Clofarabine Cytarabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of clofarabine in combination with cytarabine [ Designated as safety issue: Yes ]
Overall response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	87
Study Start Date:	March 2007
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

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

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.

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

Eligibility

Ages Eligible for Study:	1 Year to 30 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

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

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00372619

Show 21 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Bassem I. Razzouk, MD	St. Vincent Indianapolis Hospital
Investigator:	Todd Cooper, DO	University of Alabama at Birmingham

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000494654, COG-AAML0523
Study First Received:	September 6, 2006
Last Updated:	June 17, 2009
ClinicalTrials.gov Identifier:	NCT00372619 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia

Study placed in the following topic categories:

Acute Lymphoblastic Leukemia, Childhood
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors
Folate
Leukemia, Myeloid, Acute
Vitamin B9
Leukemia
Acute Myelocytic Leukemia
Methotrexate
Lymphoma
Acute Lymphoblastic Leukemia
Cytarabine
Clofarabine

Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Folic Acid Antagonists
Folinic Acid
Antiviral Agents
Immunosuppressive Agents
Recurrence
Acute Myeloid Leukemia, Childhood
Folic Acid
Lymphatic Diseases
Lymphoproliferative Disorders
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Leukemia, Myeloid, Acute
Leukemia
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Cytarabine
Clofarabine
Immunoproliferative Disorders
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Enzyme Inhibitors
Leukemia, Myeloid
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases

ClinicalTrials.gov processed this record on July 02, 2009