Clofarabine With Cytarabine for Patients With Minimal Residual Disease Positive Leukemia

NCT01158885 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: T2009-002
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

This study will test the ability of clofarabine + cytarabine to eliminate minimal residual disease (MRD) in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. The toxicity profile of this regimen will be evaluated in addition to toxicity experienced by patients who proceed to stem cell transplant. Overall length of remission will also be collected.

Conditions

Minimal Residual Disease; Leukemia, Lymphoblastic, Acute; Leukemia, Myelogenous, Acute

Keywords

relapsed; relapse; refractory; Minimal Residual disease; MRD; MRD positive; MRD+; ALL; Acute lymphoblastic leukemia; AML; Acute myelogenous leukemia; Relapsed AML

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease (MRD)

  To be assessed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patients whose bone marrows exhibit complete remission by morphology. Patient's bone marrow will be evaluated for the amount of minimal residual disease (MRD) present after treatment on courses 1 and 2.

  Sample collected between Days 22-36 of courses 1 and 2

Secondary Outcomes (2)

• Number of Patients With Dose-Limiting Toxicity (DLT)

  Beginning with the first dose of investigational product until day 56 of treatment course, an average of 1 year

• Occurrence of Toxicity During Hematopoietic Cell Transplant (HCT) for Patients Who Achieve Remission and Proceed to Transplant

  Every 3 months for life following completion of protocol therapy.

Study Arms (1)

Single Arm

EXPERIMENTAL

A maximum of two courses of the following regimen will be administered. * Clofarabine: 20 mg/m2/day intravenously (IV) over 2 hours (given at hours 0 to 2) on days 1 through 5. * Cytarabine intravenous: 1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5. * Methotrexate: to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age. * Intrathecal (IT) cytarabine: is optional for acute myelogenous leukemia (AML) patients.

Drug: Clofarabine; Drug: Cytarabine intravenous; Drug: Methotrexate; Drug: Intrathecal (IT) Cytarabine

Interventions

Clofarabine DRUG

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

Also known as: Clolar, CAFdA, Cl-F-ara-A

Single Arm

Cytarabine intravenous DRUG

1 gram/m2/day intravenously (IV) over 2 hours to be given 4 hours after the initiation of clofarabine on days 1 through 5.

Also known as: AraC, Cytosine arabinoside, Cytosar

Single Arm

Methotrexate DRUG

Methotrexate to be given intrathecally (IT) to all acute lymphoblastic leukemia (ALL) patients on day 1 at the dose defined by age below: * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age

Also known as: MTX, Amethopterin

Single Arm

Intrathecal (IT) Cytarabine DRUG

Intrathecal (IT) cytarabine is optional for acute myelogenous leukemia (AML) patients. If intrathecal cytarabine is to be given, it must be given at least 72 hours but not more than 7 days prior to the initiation of intravenous cytarabine. Dose should be given according to age as defined 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: AraC, Cytosine arabinoside, Cytosar

Single Arm

Eligibility Criteria

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

You may qualify if:

• Patients must be ≥1 and ≤ 21 years of age when enrolled onto this study.
• Diagnosis
• Patients must have a diagnosis of relapsed or refractory AML or ALL and,
• Patient must have an M1 marrow based upon a recovered marrow with less than 5% blasts by conventional morphology and,
• Patient must have minimal residual disease (MRD) detected by either multidimensional or conventional flow cytometry greater than 0.1% and less than 5% following any re-induction attempt and
• Patients must be CNS 1.
• Patient must have an ANC \>500/μL off cytokine support for at least 24 hours and platelets \>50,000 K/μL without platelet transfusion in the past seven days
• Performance Level Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤16 years of age.
• Patient must have adequate venous access.
• Prior Therapy
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• At least 21 days must have elapsed from prior chemotherapy, at least 7 days must have elapsed since receiving biological therapy.
• It must be at least 45 days from any higher dose cytarabine therapy (\>1 gm/ m2/day).
• Patients on steroid taper must be on less than 0.5mg/kg/day with plans to continue taper and discontinue the steroids.
• Renal and Hepatic Function Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:

You may not qualify if:

• Patients will be excluded if they meet any of the following criteria:
• Patients with previous HSCT within previous 180 days.
• Patients who have had prior treatment with clofarabine.
• Patients with CNS2 or CNS 3 disease or bulky chloromatous disease.
• Patients with Down Syndrome.
• Patients with a 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 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).
• Use of investigational agents within 30 days of planned treatment on this protocol.
• Patient is receiving or plans to receive concomitant chemotherapy, radiation therapy, immunotherapy or other anti-cancer therapy other than is specified in the protocol.
• 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.
• Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions:
• Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed.
• Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
• Patient has active acute (greater than grade II) or active chronic extensive GVHD. Patients who are on a tapering dose of immunosuppressants will be permitted (tapering calcineurin inhibitor and/or less than 0.5 mg/kg/day of steroids).

Sponsors & Collaborators

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

Study Sites (2)

Carolina-Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Links

• Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web site

MeSH Terms

Conditions

Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Recurrence

Interventions

Clofarabine; Cytarabine; Methotrexate

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Disease Attributes

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; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines

Limitations and Caveats

The study only enrolled two patients and closed early due to low accrual.

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

• Blythe Thomson, MD

  Seattle Children's Hospital

  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: June 30, 2010
• First Posted: July 8, 2010
• Study Start: August 1, 2010
• Primary Completion: October 24, 2012
• Study Completion: October 24, 2012
• Last Updated: October 26, 2021
• Results First Posted: October 7, 2019

Record last verified: 2021-10

Locations

US (2)