Augmented Berlin-Frankfurt-Munster Therapy Plus Ofatumumab for Young Adults With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

NCT02419469 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0396NCI-2015-00967
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if a chemotherapy combination called augmented Berlin-Frankfurt-Munster (BFM), when also combined with ofatumumab or rituximab, can help to control precursor-B ALL or LL in patients who are 12-30 years of age. The safety of these drug combinations will also be studied. Augmented BFM is made up of daunorubicin, vincristine, prednisone, dexamethasone, PEG asparaginase, and methotrexate.

Conditions

Leukemia; Precursor-B Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma; Lymphoma

Keywords

Leukemia; Precursor-B acute lymphoblastic leukemia; ALL; Lymphoblastic lymphoma; LL; Lymphoma; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Daunorubicin; Daunorubicin Hydrochloride; Cerubidine; Daunomycin; DNR; Vincristine; Prednisone; PEG asparaginase; Pegaspargase; Oncaspar; Polyethylene glycol conjugated lasparaginase-H; Ofatumumab; Arzerra; Rituximab; Rituxan; Methotrexate; Cyclophosphamide; Cytoxan; Neosar; Mercaptopurine; 6-mercaptopurine; Purinethol; 6-MP; Doxorubicin; Doxorubicin hydrochloride; Adriamycin PFS; Adriamycin RDF; Adriamycin; Rubex; Dexamethasone; Decadron; Thioguanine; 6-thioguanine

Outcome Measures

Primary Outcomes (1)

• Event Free Survival (EFS)

  Event free survival defined as the time from treatment to relapse of leukemia or death for any reason or lost to follow-up. Study regimen considered successful if it exhibits a 3-year EFS rate greater than 65% and response rate no less than 90% with Grade III-IV infectious toxicity rate in induction no more than 33%.

  3 years

Study Arms (1)

Augmented BFM Therapy + Ofatumumab or Rituximab

EXPERIMENTAL

Participants receive the study drugs in Induction, Consolidation, and Maintenance Courses.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Vincristine; Drug: Prednisone; Drug: PEG asparaginase; Drug: Ofatumumab; Drug: Rituximab; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: Mercaptopurine; Drug: Doxorubicin; Drug: Dexamethasone acetate; Drug: Thioguanine

Interventions

Cytarabine DRUG

Participants initially receive intrathecal treatment using Cytarabine 100 mg on Day 1. Induction chemotherapy must begin within 3 days of the intrathecal Cytarabine dose. Consolidation Therapy 1: Cytarabine 75 mg/m2 subcutaneously Days 1 - 4 and 8 - 11. Consolidation Therapy 3B: Cytarabine 75 mg/m2 subcutaneously Days 1 - 4 and Days 8 - 11.

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Augmented BFM Therapy + Ofatumumab or Rituximab

Daunorubicin DRUG

Induction Therapy: Daunorubicin 25 mg/m2 by vein weekly for 4 doses.

Also known as: Daunorubicin Hydrochloride, Cerubidine, Daunomycin, DNR

Augmented BFM Therapy + Ofatumumab or Rituximab

Vincristine DRUG

Induction Therapy: Vincristine 1.5 mg/m2 by vein weekly for 4 doses. Consolidation Therapy 1: Vincristine 1.5 mg/m2 by vein Week 3 and Week 4. Consolidation Therapy 2: Vincristine 1.5 mg/m2 by vein every 10 days for 5 doses. Consolidation Therapy 3A: Vincristine 1.5 mg/m2 by vein weekly for 3 doses. Consolidation Therapy 3B: Vincristine 1.5 mg/m2 by vein Weeks 3 and 4. Maintenance Therapy (24 months): Vincristine 1.5 mg/m2 by vein every 28 days.

Augmented BFM Therapy + Ofatumumab or Rituximab

Prednisone DRUG

Induction Therapy: Prednisone 60 mg/m2/day by mouth for 28 days.

Augmented BFM Therapy + Ofatumumab or Rituximab

PEG asparaginase DRUG

Induction Therapy: PEG asparaginase 2000 IU/m2 by vein on Day 4 of induction. Consolidation Therapy 1: PEG-asparaginase 2000 IU/m2 by vein Week 3 and Week 7. Consolidation Therapy 2: PEG-asparaginase 2000 IU/m2 by vein Weeks 1 and 4. Consolidation Therapy 3A: PEG-asparaginase 2000 IU/m2 by vein in Week 1. Consolidation Therapy 3B: PEG-asparaginase 2000 IU/m2 by vein Week 3.

Also known as: Pegaspargase, Oncaspar, Polyethylene Glycol Conjugated Lasparaginase-H

Augmented BFM Therapy + Ofatumumab or Rituximab

Ofatumumab DRUG

Induction Therapy: Ofatumumab 300 mg by injection or vein on Day 2 and Ofatumumab 2000 mg by injection or vein on Day 15. Consolidation Therapy 1: Ofatumumab 2000 mg by injection or vein Week 1 and Week 5. Consolidation Therapy 2: Ofatumumab 2000 mg by injection or vein Week 1 and Week 5. Consolidation Therapy 3A: Ofatumumab 2000 mg by injection or vein Week 1 and Week 3.

Also known as: Arzerra

Augmented BFM Therapy + Ofatumumab or Rituximab

Rituximab DRUG

Induction Therapy: If Ofatumumab not available, Rituximab 375 mg/m2 by vein on Day 1 and on Day 15. Consolidation Therapy 1: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 5. Consolidation Therapy 2: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 5. Consolidation Therapy 3A: If Ofatumumab not available, Rituximab 375 mg/m2 by vein Week 1 and Week 3.

Also known as: Rituxan

Augmented BFM Therapy + Ofatumumab or Rituximab

Methotrexate DRUG

Induction Therapy: Intrathecal methotrexate 12 mg on Day 8 and Day 29. Consolidation Therapy 1: Intrathecal methotrexate 12 mg Weekly, Weeks 1 - 4. Consolidation Therapy 2: Methotrexate by vein every 10 days starting at 100 mg/m2 and increasing by 50 mg/m2 as tolerated. and Intrathecal methotrexate 12 mg Week 1. Consolidation Therapy 3A: Intrathecal methotrexate 12 mg in Week 1. Consolidation Therapy 3B: Intrathecal methotrexate 12 mg Week 1 and 2. Maintenance Therapy (24 months): Methotrexate 20 mg/m2 by mouth weekly, hold on days of intrathecal methotrexate. Maintenance Therapy (24 months): Intrathecal methotrexate 12 mg every 3 months for 4 doses.

Augmented BFM Therapy + Ofatumumab or Rituximab

Cyclophosphamide DRUG

Consolidation Therapy 1: Cyclophosphamide 1 gram/m2 by vein Week 1 and Week 5. Consolidation Therapy 3B: Cyclophosphamide 1 gram/m2 by vein Week 1.

Also known as: Cytoxan, Neosar

Augmented BFM Therapy + Ofatumumab or Rituximab

Mercaptopurine DRUG

Consolidation Therapy 1: Mercaptopurine 60 mg/m2/day by mouth Days 1 - 14. Maintenance Therapy (24 months): Mercaptopurine 75 mg/m2 by mouth nightly.

Also known as: 6-Mercaptopurine, Purinethol, 6-MP

Augmented BFM Therapy + Ofatumumab or Rituximab

Doxorubicin DRUG

Consolidation Therapy 3A: Doxorubicin 25 mg/m2 by vein weekly for 3 doses.

Also known as: Doxorubicin Hydrochloride, Adriamycin PFS, Adriamycin RDF, Adriamycin, Rubex

Augmented BFM Therapy + Ofatumumab or Rituximab

Dexamethasone acetate DRUG

Consolidation Therapy 3A: Dexamethasone 10 mg/m2 by mouth on Days 1 - 7 and Days 15 - 21. Maintenance Therapy (24 months): Dexamethasone 6 mg/m2/day by mouth Days 1 - 5 every 28 days.

Also known as: Decadron

Augmented BFM Therapy + Ofatumumab or Rituximab

Thioguanine DRUG

Consolidation Therapy 3B: Thioguanine 60 mg/m2/day by mouth for 14 days.

Also known as: 6-thioguanine

Augmented BFM Therapy + Ofatumumab or Rituximab

Eligibility Criteria

• Age: 12 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have precursor-B lymphoblastic leukemia or lymphoma.
• Patients must be untreated or have had only one prior chemotherapy regimen for ALL or LL . Previously treated patients will be analyzed separately.
• Age between 12 to 30 years old
• Patients with central nervous system (CNS) disease or testicular disease are eligible.
• Intrathecal therapy with cytarabine is allowed prior to registration for patient convenience. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin within 72 hours of the first intrathecal treatment.
• Signed informed consent prior to the start of systemic therapy. In the event of enrollment of a minor patient, an attempt to obtain assent from the patient must be documented, and parental consent must be signed.
• Echocardiogram should be done within 7 days of starting therapy if there are cardiac risk factors (e.g., history of hypertension or of myocardial infarction)
• Creatinine should be \< 3 mg/dL bilirubin \< 3 mg/dl unless due to disease
• Zubrod Performance status of \<3
• Patients who received steroids more than 72 hours prior to study enrollment are eligible but will be analyzed separately.
• Lymphoblasts may have any positive expression of cluster of differentiation antigen 20 (CD20) for ofatumumab administration.

You may not qualify if:

• Age less than twelve years of age or greater than 30 years.
• More than one prior treatment regimen for ALL or LL.
• The patient is pregnant or unwilling to practice appropriate birth control.
• Presence of the Philadelphia chromosome t(9;22)
• Laboratory or clinical evidence of active infectious hepatitis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Interventions

Cytarabine; Daunorubicin; Vincristine; Prednisone; pegaspargase; ofatumumab; Rituximab; Methotrexate; Cyclophosphamide; Mercaptopurine; Doxorubicin; dexamethasone acetate; Calcium Dobesilate; Thioguanine

Condition Hierarchy (Ancestors)

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)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds; Sulfur Compounds; Purines; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids

Results Point of Contact

• Title: Rytting,Michael E.,M.D. / PEDIATRICS
• Organization: UT MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Michael E. Rytting, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 17, 2015
• Study Start: November 13, 2015
• Primary Completion: June 22, 2017
• Study Completion: June 22, 2017
• Last Updated: June 11, 2018
• Results First Posted: June 11, 2018

Record last verified: 2018-05

Locations

US (1)