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Four Drug Reinduction With Bortezomib for Relapsed or Refractory ALL or LL in Children and Young Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02535806
Recruitment Status : Terminated (Funding source discontinued)
First Posted : August 31, 2015
Results First Posted : August 13, 2019
Last Update Posted : August 13, 2019
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Keith August, Children's Mercy Hospital Kansas City

Brief Summary:
This is a phase II study designed to investigate the combination of bortezomib with the mitoxantrone reinduction regimen used in the ALL R3 trial. The study will enroll patients with high risk ALL relapse including early bone marrow relapse and second or greater relapse of any kind. Patients with relapsed LL will also be eligible. Bone marrow evaluation will be performed after blood counts recover to assess the rate of CR (<5% bone marrow blasts) and MRD status in children following this regimen. Further treatment with or without HSCT will be at the discretion of the primary physician.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Drug: Velcade Drug: Methotrexate Drug: Methotrexate / Hydrocortisone / Cytarabine Drug: Dexamethasone Drug: Mitoxantrone Drug: Vincristine Drug: Pegaspargase Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Mitoxantrone-Based Four Drug Reinduction in Combination With Bortezomib for Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma in Children and Young Adults
Study Start Date : July 2015
Actual Primary Completion Date : May 25, 2017
Actual Study Completion Date : May 25, 2017

Arm Intervention/treatment
Experimental: Treatment Arm

Velcade will be given IV push on days 1,4,8 and 11 at a dose of 1.3 mg/m2/dose. At least 72 hours must have relapsed between doses.

IT Methotrexate (CNS Negative patients only) on days 1 and 8; age based dosing IT Methotrexate/Hydrocortisone/AraC (CNS positive patients only) on days 1, 8, 15 and 22; age based dosing.

Dexamethasone: Days 1-5 and 15-19; 10mg/m2/dose PO BID. Mitoxantrone: Days 1 and 2; 10mg/m2/dose Vincristine: days 1, 8, 15, and 22 at 1.5 mg/m2 (Maximum dose 2 mg) PEG-asparaginase: Days 3 and 17, 2500 IU/m2/dose

Drug: Velcade
4 doses of study drug will be given.
Other Name: Bortezomib

Drug: Methotrexate
Intrathecal dose For CNS negative patients, Day 1 and Day 8

Drug: Methotrexate / Hydrocortisone / Cytarabine
Intrathecal dose for CNS positive patients, Day 1, 8, 15, 22

Drug: Dexamethasone
Days 1-5 and 15-19

Drug: Mitoxantrone
Days 1 and 2

Drug: Vincristine
Days 1, 8, 15, 22

Drug: Pegaspargase
Days 3 and 17

Primary Outcome Measures :
  1. Number of Subject With Adverse Events [ Time Frame: 36 days ]
    Toxicities were assessed and graded according to CTCAE v 4.0.

Secondary Outcome Measures :
  1. Remission Rate Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL. [ Time Frame: 36 days ]
    Number of patients with bone marrow blast percentage <5% after treatment

  2. Post-induction Level of Minimal Residual Disease Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL. [ Time Frame: 36 days ]
    Percent of Cells Positive for Minimal residual disease measured by multiparameter flow cytometry

  3. 2-year Overall Survival Seen With Using Bortezomib in Combination With the ALL R3 Re-induction Regimen in Pediatric Patients With Relapsed or Refractory ALL or LL. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Eligibility Criteria

  • Age: > 1 and < 40 years of age at the time of enrollment
  • Diagnosis: Precursor B-cell ALL with bone marrow (BM) or combined BM/extramedullary relapse; T-cell ALL with relapsed disease; LL with relapsed disease, or ALL(T or pre-B) with primary refractory disease after at least two regimens
  • Performance Score: 50% for patients
  • Prior Therapy Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study.

Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. In addition, the following requirements must be met:

Cytotoxic therapy: At least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy.

Biologic (anti-neoplastic) agent: At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI).

Stem cell transplant or rescue: No evidence of active graft-vs-host disease (GVHD) and ≥ 4 months must have elapsed from time of transplant. Must not be receiving GVHD prophylaxis.

  • Adequate Organ Function Requirements
  • Reproductive Function: Female patients of childbearing potential must have a negative pregnancy test confirmed within 2 weeks prior to enrollment, must agree not to breastfeed their infants while on this study.Male and female patients of child-bearing potential must agree to use 2 effective methods of contraception approved by the investigator, at the same time, from the time of signing the informed consent form and for a minimum of 6 months after study treatment, or agree to completely abstain from heterosexual intercourse.
  • Signed written informed consent. Assent from children will be obtained per institutional guidance.

Exclusion Eligibility Criteria

  • known allergy to any of the drugs on the study with the exception of PEG-asparaginase
  • Isolated CNS or isolated testicular disease
  • Systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
  • Known optic nerve and/or retinal involvement
  • Patients with concomitant genetic syndrome
  • Cumulative prior anthracycline exposure must not exceed 400 mg/m2
  • Patients who have previously received bortezomib or other proteasome inhibitors
  • Patients taking anticonvulsants known to activate the cytochrome p450 system
  • Patients who cannot receive any asparaginase products
  • Patients who are pregnant or breast-feeding
  • Patients with planned non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
  • Significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
  • Patients with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Diagnosed or treated for another malignancy within 2 years of enrollment
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.Radiation therapy within 3 weeks before randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02535806

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United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Sponsors and Collaborators
Children's Mercy Hospital Kansas City
Millennium Pharmaceuticals, Inc.
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Principal Investigator: Keith J August, MD Children's Mercy Hospital Kansas City
  Study Documents (Full-Text)

Documents provided by Keith August, Children's Mercy Hospital Kansas City:
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Responsible Party: Keith August, Principal Investigator, Children's Mercy Hospital Kansas City
ClinicalTrials.gov Identifier: NCT02535806    
Other Study ID Numbers: MERCY01
First Posted: August 31, 2015    Key Record Dates
Results First Posted: August 13, 2019
Last Update Posted: August 13, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We hope to publish results

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Keith August, Children's Mercy Hospital Kansas City:
Relapsed, Refractory
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Abortifacient Agents, Nonsteroidal