T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML)

NCT00939653 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: T2007-002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating children (age 1-21) with leukemia. This research study will use clofarabine with two other cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and cyclophosphamide (Cytoxan®).

Conditions

Relapsed Acute Myelogenous Leukemia

Keywords

relapsed; relapse; refractory; AML; Acute myelogenous leukemia; Relapsed AML

Outcome Measures

Primary Outcomes (2)

• Achievement of Complete Remission (CR) at Reinduction

  Disease response assessed after chemotherapy from bone marrow aspirates/biopsies and complete blood count.

  Between Days 22-36 or on Day 43 and weekly thereafter if peripheral counts haven't recovered

• Death

  Number of participants who died.

  From the first dose of study therapy until 30 days after last therapy dose

Study Arms (1)

Single Arm - Clofarabine with Chemo

EXPERIMENTAL

All patients receive the same treatment regimen consisting of clofarabine, etoposide, cyclophosphamide, cytarabine, and filgrastim. Up to 4 courses of therapy may be given.

Drug: Clofarabine; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Filgrastim; Drug: Cytarabine

Interventions

Clofarabine DRUG

40 mg/m2/day IV over 2 hours (given at hours 0 to 2) on days 1 through 5.

Also known as: Clolar

Single Arm - Clofarabine with Chemo

Etoposide DRUG

100 mg/m2/day IV over 2 hours (given at hours 2 to 4) on days 1 through 5.

Also known as: VP-16, VePesid, Etopophos

Single Arm - Clofarabine with Chemo

Cyclophosphamide DRUG

440 mg/m2/day IV as a 30-60 minute infusion (given at hours 4 to 5) on days 1 through 5.

Also known as: Cytoxan

Single Arm - Clofarabine with Chemo

Filgrastim DRUG

Administered in Courses 1 and 2 only. 5 micrograms/kg/day IV or SC will begin on Day 6 and end when the ANC is \> 1000 x 2 days.

Also known as: Neupogen, G-CSF, GCSF, Granulocyte Colony Stimulating Factor

Single Arm - Clofarabine with Chemo

Cytarabine DRUG

Given intrathecally on day 1 at the dose defined by age below: 30 mg for patients age 1-1.99 50 mg for patients age 2-2.99 70 mg for patients \>3 years of age

Also known as: Cytosine Arabinoside, Ara-C, Cytosar, AraC

Single Arm - Clofarabine with Chemo

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: patients must be ≥ 1 and ≤ 21 years of age at the of study entry.
• Diagnosis:
• Patients must have a diagnosis of first or second relapse or refractory acute myelogenous leukemia (AML) according to WHO classification with ≥ 5% blasts in the bone marrow, with or without extramedullary disease.
• Patients may have CNS 1 or CNS 2 disease but not CNS 3.
• Performance Level: Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age.
• Prior Therapy:
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Patient has not received more than 2 previous induction attempts. (Frontline therapy is included in this count).
• Patients must have adequate venous access.
• At least 1 year must have elapsed since hematopoietic stem cell transplant (HSCT) and patients must not have active GVHD.
• Reproductive Function
• Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 2 weeks prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
• Renal and Hepatic Function:

You may not qualify if:

• Patients with Down Syndrome.
• Prior treatment with Clofarabine.
• Previous history of veno-occlusive disease (VOD) or findings consistent with a diagnosis of VOD, defined as: conjugated serum bilirubin \> 1.4 mg/dL AND unexplained weight gain greater than 10% of baseline weight or ascites AND hepatomegaly or right upper quadrant pain without another explanation, OR reversal of portal vein flow on ultrasound, OR pathological confirmation of VOD on liver biopsy.
• Patients who have a history of cirrhosis of the liver or who are positive for hepatitis B core antibody (anti-HBc) or have a positive test for hepatitis C antibody (anti-HCV).
• Patient has received TBI.
• If it has been less than 1 year since the patient had a HSCT.
• Infection Criteria
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Positive blood culture within 48 hours of study registration.
• Patient required supplemental oxygen or vasopressors within 48 hours of study (Oxygen after anesthesia for procedures is ok).
• Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before planned drug initiation with the exception of hydroxyurea or intrathecal therapy given with the diagnostic lumbar puncture.
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
• Pregnant or lactating patients.
• Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (4)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of Miami Cancer Center

Miami, Florida, 33136, United States

Location

Children's Memorial

Chicago, Illinois, 60611, United States

Location

Childrens Hospital & Clinics of Minnesota

Minneapolis, Minnesota, 55404-4597, United States

Location

Related Links

• For more information about this and other clinical trials, please visit the TACL website.

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Clofarabine; Etoposide; etoposide phosphate; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Trial was terminated early due to loss of funding and concern that accrual goals could not be met. All six patients enrolled were deemed evaluable toxicity. No analysis was conducted on the study outcome variables.

Results Point of Contact

• Title: Peggy Romano, BA, CCRP
• Organization: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles

promano@chla.usc.edu

323-361-5505

Study Officials

• Paul Gaynon, MD

  Children's Hospital Los Angeles

  STUDY CHAIR

• Nobuko Hijiya, MD

  Ann & Robert H Lurie Children's Hospital of Chicago

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2009
• First Posted: July 15, 2009
• Study Start: July 10, 2009
• Primary Completion: July 15, 2011
• Study Completion: July 15, 2011
• Last Updated: February 19, 2020
• Results First Posted: February 19, 2020

Record last verified: 2020-02

Locations

US (4)