Clofarabine and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia, or Myeloproliferative Disorders

NCT00293410 | Completed Phase 1

• 4 other identifiers: J0561 CDR0000456431P30CA006973JHOC-J0561JHOC-00000845
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cyclophosphamide, 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 trial is studying the side effects and best dose of clofarabine and cyclophosphamide in treating patients with relapsed or refractory acute leukemia, chronic myelogenous leukemia, or myeloproliferative disorders.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Myelodysplastic/Myeloproliferative Diseases

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; accelerated phase chronic myelogenous leukemia; chronic idiopathic myelofibrosis; chronic myelomonocytic leukemia; juvenile myelomonocytic leukemia; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; acute undifferentiated leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute promyelocytic leukemia (M3); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); childhood acute basophilic leukemia; childhood acute monocytic leukemia (M5b); childhood acute eosinophilic leukemia; childhood acute erythroleukemia (M6); childhood acute megakaryocytic leukemia (M7); childhood acute minimally differentiated myeloid leukemia (M0); childhood acute myeloblastic leukemia with maturation (M2); childhood acute myeloblastic leukemia without maturation (M1); childhood acute myelomonocytic leukemia (M4); childhood acute monoblastic leukemia (M5a); childhood acute promyelocytic leukemia (M3)

Interventions

clofarabine DRUG

cyclophosphamide DRUG

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed leukemia or myeloproliferative disorders, including 1 of the following: * Acute myeloid leukemia (AML) of any subtype * Treatment-related AML OR AML evolving from myeloproliferative disorders (MPD) or transformed from myelodysplastic syndrome * Acute lymphocytic leukemia * Acute progranulocytic leukemia * Must not be eligible for arsenic or retinoic acid therapy * Chronic myelogenous leukemia in accelerated phase or blast crisis * High-risk MPD, including any of the following: * Myelofibrosis * Chronic myelomonocytic leukemia with 5%-19% blasts * Relapsed or refractory juvenile myelomonocytic leukemia * Relapsed and/or refractory disease with progressive disease since last therapy * No more than 3 prior induction regimens with cytotoxic agents for adults * Must be in second relapse for patients \< 21 years of age PATIENT CHARACTERISTICS: * ECOG performance status 0-2 (for adults) OR Lansky 50-100% (for pediatric patients) * Bilirubin ≤ 1.5 mg/dL (may be elevated due to hemolysis in adult patients) * AST and ALT ≤ 5 times upper limit of normal * Creatinine ≤ 2.0 mg/dL (for adults) * Normal renal function (for pediatric patients) * Cardiac function normal as measured by MUGA scan or echocardiogram * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for at least 6 months after completion of study treatment * HIV negative * No active graft-versus-host disease ≥ grade 2 * No active, uncontrolled infection * No fever * No unstable CT scans of the lungs, sinuses, or abdomen within the past 4 weeks * No arrhythmias (other than atrial flutter or fibrillation) requiring medication * No dyspnea at rest or with minimal exertion * No uncontrolled congestive heart failure * No myocardial infarction within the past 3 months * No history of severe coronary artery disease * No other significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance or interfere with consent, study participation, follow up, or interpretation of study results PRIOR CONCURRENT THERAPY: * Must have recovered from all acute toxic effects from prior treatment * More than 30 days since prior investigational cytotoxic agents * At least 3 days since prior azacitidine, thalidomide, hydroxyurea, imatinib mesylate, or interferon * At least 1 week since prior growth factors except epoetin alfa * More than 3 weeks since any other prior anticancer therapy * No concurrent chemotherapy, radiotherapy, or immunotherapy * No other concurrent anticancer investigational or commercial agents * No routine prophylactic use of a colony-stimulating factor (filgrastim \[G-CSF\] or sargramostim \[GM-CSF\]) * Therapeutic use of colony-stimulating factors may be considered at the discretion of the investigator * No prolonged use of corticosteroids to prevent or treat emesis or as a chemotherapeutic agent

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• Karp JE, Ricklis RM, Balakrishnan K, Briel J, Greer J, Gore SD, Smith BD, McDevitt MA, Carraway H, Levis MJ, Gandhi V. A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias. Blood. 2007 Sep 15;110(6):1762-9. doi: 10.1182/blood-2007-03-081364. Epub 2007 Jun 11.

  PMID: 17562873 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Myelodysplastic-Myeloproliferative Diseases; Congenital Abnormalities; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Accelerated Phase; Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute; Blast Crisis; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

Clofarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Judith E. Karp, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 16, 2006
• First Posted: February 17, 2006
• Study Start: November 1, 2005
• Primary Completion: April 1, 2010
• Last Updated: May 6, 2010

Record last verified: 2010-05

Locations

US (1)