Bridging Study to Eliminate Presence of MRD for Acute Leukemia Before HCT

Study Overview
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Brief Summary
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This is a Phase 2 study designed for the purpose of estimating various parameters surrounding the efficacy of Clofarabine, Cyclophosphamide and Etoposide in eliminating minimal residual disease (MRD) in acute leukemia patients otherwise in remission and without causing significant delay of HCT due to treatment related toxicity. A single course of bridge chemotherapy is given prior to the transplant procedure as an approach to improved disease-free survival in a patient group who historically has had inferior outcomes.

Detailed Description
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Study entry is open to patients regardless of gender or ethnic background. The intent of this study design is for all patients to receive and complete one course of therapy. Patients who exhibit signs of disease progression or experience an unacceptable toxicity will be discontinued from treatment. There will be no dose delays or dose reductions of study drugs for hematologic toxicity during Consolidation Bridging therapy (Day 1 through Day 30); however, prolonged hematopoietic recovery or bone marrow aplasia during the first 42 days may meet a study stopping rule.

Official Title
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Bridging Study: A Phase 2 Study Investigating Clofarabine, Cyclophosphamide and Etoposide for Children, Adolescents, and Young Adults (AYA) With Acute Leukemia and Minimal Residual Disease

Conditions
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Acute Myeloid Leukemia, Leukemia, Acute Lymphoblastic

Intervention / Treatment
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* Drug: Clofarabine
* Drug: Cyclophosphamide
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 (≥ 0.01% leukemic blasts for ALL or ≥ 0.5% 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 (HCT) independent of this study Patients must have an available donor and have intention of proceeding directly to ALL-HCT after completion of 1 cycle of Bridging therapy. Age 0 to 39 years Karnofsky Performance Status ≥ 50% for patients 16 years and older and Lansky Play Score ≥ 50 for patients under 16 years of age (see Appendix 2) 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 ≥ 60 mL/min/1.73 m2 or serum creatinine based on age/gender as follows: Hepatic: 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 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 7 days must have elapsed from prior chemotherapy. 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. Exclusion Criteria: Acute Promyelocytic Leukemia (APL) Active extramedullary disease (CNS ≥ CNS2 and/or testicular leukemia) or presence of chloromatous disease Receiving 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 Participating in a concomitant Phase 1 or 2 study

Ages Eligible for Study
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Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bridging Arm<br>Days 1-5 Receive 20 mg/m2 IV Clofarabine (CLOLAR) over 2 hours followed by 100 mg/m2 IV Etoposide (VP-16, Etopophos) over 2 hours followed by 300 mg/m2 IV Cyclophosphamide (Cytoxan, CTX) as a 30-60 minute infusion | Drug: Clofarabine<br>* Days 1-5 receive Clofarabine 20 mg/m2 IV over 2 hours<br>* Other names: CLOLAR;Drug: Cyclophosphamide<br>* Days 1-5 receive Cyclophosphamide 300 mg/m2 IV as a 30-60 minute infusion<br>* Other names: Cytoxan, CTX;Drug: Etoposide<br>* Days 1-5 receive Etoposide 100 mg/m2 IV over 2 hours<br>* Other names: VP-16, Etopophos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal Residual Disease | A bone marrow evaluation to determine study response and remission status will be performed on study Day 30 or upon adequate blood count recovery (ANC > 0.50 and platelet > 50,000), whichever occurs first. If the marrow is hypocellular and without evidence of normal tri-lineage hematopoiesis the marrow should be repeated at Day 42. | Day 30 or adequate blood recovery |