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

NCT02535806 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: MERCY01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma

Keywords

Relapsed, Refractory

Outcome Measures

Primary Outcomes (1)

• Number of Subject With Adverse Events

  Toxicities were assessed and graded according to CTCAE v 4.0.

  36 days

Secondary Outcomes (3)

• 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.

  36 days

• 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.

  36 days

• 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.

  2 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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; Drug: Methotrexate; Drug: Methotrexate / Hydrocortisone / Cytarabine; Drug: Dexamethasone; Drug: Mitoxantrone; Drug: Vincristine; Drug: Pegaspargase

Interventions

Velcade DRUG

4 doses of study drug will be given.

Also known as: Bortezomib

Treatment Arm

Methotrexate DRUG

Intrathecal dose For CNS negative patients, Day 1 and Day 8

Treatment Arm

Methotrexate / Hydrocortisone / Cytarabine DRUG

Intrathecal dose for CNS positive patients, Day 1, 8, 15, 22

Treatment Arm

Dexamethasone DRUG

Days 1-5 and 15-19

Treatment Arm

Mitoxantrone DRUG

Days 1 and 2

Treatment Arm

Vincristine DRUG

Days 1, 8, 15, 22

Treatment Arm

Pegaspargase DRUG

Days 3 and 17

Treatment Arm

Eligibility Criteria

• Age: 1 Year - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Bortezomib; Methotrexate; Hydrocortisone; Cytarabine; Dexamethasone; Mitoxantrone; Vincristine; pegaspargase

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Steroids, Fluorinated; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Keith August
• Organization: Children's Mercy Hospital

kjaugust@cmh.edu

816-302-6808

Study Officials

• Keith J August, MD

  Children's Mercy Hospital Kansas City

  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: Principal Investigator

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 31, 2015
• Study Start: July 1, 2015
• Primary Completion: May 25, 2017
• Study Completion: May 25, 2017
• Last Updated: August 13, 2019
• Results First Posted: August 13, 2019

Record last verified: 2019-07

Locations

US (1)