Clofarabine, Cyclophosphamide and Etoposide for Minimal Residual Disease Positive Acute Leukemia

NCT01677949 | Withdrawn Phase 2 DMC

• 2 other identifiers: 2011LS158HM2012-05
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Study Design: This is a two-stage Phase II trial investigating the efficacy of Clofarabine, Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the study treatment in eliminating the presence of minimal residual disease without causing a significant delay of allo-HCT due to treatment related toxicity. The intent of this study is to allow patients to proceed to transplant (independent of this study) within 42 days of Day 1 of Clofarabine based therapy.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Patients Unable to Proceed to Transplantation

  The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (\<0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.

  Between Day 30 and Day 42

Secondary Outcomes (5)

• Rate of Pre-Transplant Chemotherapy-Induced Aplasia

  After Day 42

• Rate of Infectious Complications

  Day 1 Through Day 30

• Treatment-Related Mortality After Transplant

  Day 100

• Disease-Free Survival After Transplant

  1 Year

• Rate of Leukemic Relapse After Transplant

  Day 100

Study Arms (2)

ALL patients receiving transplant

EXPERIMENTAL

Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute lymphoblastic leukemia (ALL) along with Clofarabine, Etoposide and Cyclophosphamide.

Drug: Clofarabine; Drug: Etoposide; Drug: Cyclophosphamide; Biological: allogeneic hematopoietic cell transplantation

AML patients receiving transplant

EXPERIMENTAL

Patients intent on receiving an allogeneic hematopoietic cell transplantation (allo-HCT) with the diagnosis of acute myeloid leukemia (AML) along with Clofarabine, Etoposide and Cyclophosphamide.

Drug: Clofarabine; Drug: Etoposide; Drug: Cyclophosphamide; Biological: allogeneic hematopoietic cell transplantation

Interventions

Clofarabine DRUG

Days 1-5: Clofarabine 30 mg/m\^2 for 0-30 years of age or 20 mg/m\^2 for \> 30 years of age intravenously (IV) over 2 hours

Also known as: Clolar

ALL patients receiving transplant; AML patients receiving transplant

Etoposide DRUG

Days 1-5: Etoposide 100mg/m\^2 IV over 2 hours

Also known as: Eposin, Etopophos, Vepesid, VP-16

ALL patients receiving transplant; AML patients receiving transplant

Cyclophosphamide DRUG

Days 1-5: Cyclophosphamide 300 mg/m\^2 as a 30-60 minute infusion

Also known as: Cytoxan

ALL patients receiving transplant; AML patients receiving transplant

allogeneic hematopoietic cell transplantation BIOLOGICAL

Between Days 28 and 42: infused independent of this study

Also known as: allo-HCT

ALL patients receiving transplant; AML patients receiving transplant

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) with \<5% blasts in the bone marrow (M1) by morphology and that meets one of the following criteria:
• Flow cytometric evidence of MRD (≥ 0.1% leukemic blasts for ALL or \<5% leukemic blasts for AML detected in the bone marrow) OR
• Molecular/cytogenetic evidence of disease (FISH or PCR methodology) performed within 7 days
• AND with the intent of going on to an allogeneic hematopoietic cell transplantation (allo-HCT) independent of this study
• Age 0 to 60 years
• Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play Score ≥ 50 for patients under 16 years of age
• Patients must have a life expectancy ≥ 8 weeks as determined by the enrolling investigator
• Have acceptable organ function as defined within 7 days of study registration:
• Renal: creatinine clearance ≥70mL/min/1.73m2 or serum creatinine based on age/gender
• Hepatic: aspartate aminotransferase (ALT) \< 5 x upper limit of normal (ULN) and total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
• Cardiac: left ventricular ejection fraction ≥ 40% by echocardiogram (ECHO/MUGA)
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 days must have elapsed from prior chemotherapy; at least 7 days must have elapsed since receiving biological therapy.
• Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor and at least 14 days since pegfilgrastim (Neulasta®) administration.
• Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the last dose of chemotherapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the last dose of chemotherapy.
• Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

You may not qualify if:

• Acute Promyelocytic Leukemia (APL)
• Active central nervous system (CNS) leukemia or known chloromatous disease
• Receiving or plans to receive concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy other than is specified in the protocol
• 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)
• Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
• Known allergy to any of the agents or their ingredients used in this study

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Clofarabine; Etoposide; etoposide phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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

Study Officials

• Michael Burke, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2012
• First Posted: September 3, 2012
• Study Start: December 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: December 2, 2017

Record last verified: 2016-04

Locations

US (1)