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

NCT02349178 | Terminated Phase 2 Results DMC

• 1 other identifier: Bridging
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Leukemia, Acute Lymphoblastic; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Bridging Arm

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Etoposide

Interventions

Clofarabine DRUG

Days 1-5 receive Clofarabine 20 mg/m2 IV over 2 hours

Also known as: CLOLAR

Bridging Arm

Cyclophosphamide DRUG

Days 1-5 receive Cyclophosphamide 300 mg/m2 IV as a 30-60 minute infusion

Also known as: Cytoxan, CTX

Bridging Arm

Etoposide DRUG

Days 1-5 receive Etoposide 100 mg/m2 IV over 2 hours

Also known as: VP-16, Etopophos

Bridging Arm

Eligibility Criteria

• Age: Up to 39 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 (≥ 0.01% 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• American Family Children's Hospital: collaborator
• Nationwide Children's Hospital: collaborator

Study Sites (4)

Nationwide Children's Hospital

Columbus, Ohio, 53205, United States

Location

American Family Children's Hospital

Madison, Wisconsin, 53792, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

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

Interventions

Clofarabine; Cyclophosphamide; Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

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

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; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Michael J Burke, MD
• Organization: Medical College of Wisconsin

mmburke@mcw.edu

414-955-4170

Study Officials

• Michael J Burke, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: January 28, 2015
• Study Start: December 8, 2014
• Primary Completion: March 16, 2017
• Study Completion: March 16, 2017
• Last Updated: March 9, 2020
• Results First Posted: February 12, 2019

Record last verified: 2020-02

Locations

US (4)