Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma

NCT02293109 | Completed Phase 1 DMC

• 3 other identifiers: 660258UCDCC#246NCI-2014-02245
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of carfilzomib when given together with the hyperfractionated (hyper)-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (CVAD) chemotherapy regimen in treating patients with newly diagnosed acute lymphoblastic leukemia or lymphoma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib with combination chemotherapy may kill more cancer cells.

Conditions

Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of carfilzomib with hyper-CVAD, defined as the dose that produces dose limiting toxicity in 17% or fewer (1/6) of patients, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4

  The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

  Up to 56 days (after second course)

Secondary Outcomes (3)

• Rate of remission

  Up to 56 days (after second course)

• Rate of minimal residual disease (MRD) in bone marrow aspirate samples

  Up to 56 days (after second course)

• Rate of MRD in bone marrow aspirate samples

  Up to 112 days (after 4th course)

Study Arms (1)

Treatment (carfilzomib and hyper-CVAD)

EXPERIMENTAL

Patients receive carfilzomib IV over 30 minutes on days 0, 1, 7, and 8. Patients also receive hyper-CVAD comprising cyclophosphamide IV over 2 hours every 12 hours for 6 doses beginning on day 1, vincristine sulfate IV on days 4 and 11, doxorubicin hydrochloride IV over 2-24 hours on day 4, and dexamethasone PO on days 1-4 and 11-14 (courses 1 and 3) and methotrexate IV over 24 hours on day 1, cytarabine IV over 2 hours every 12 hours for 4 doses starting on day 2, leucovorin calcium IV or PO every 6 hours beginning 36 hours after the start of methotrexate infusion, and methylprednisolone IV every 12 hours for 6 doses beginning on day 1 (courses 2 and 4). Patients with CD20 positive disease also receive rituximab twice daily on days 1 and 11 of courses 1 and 3 and days 1 and 8 of courses 2 and 4. Treatment repeats every 3-4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Drug: carfilzomib; Drug: cyclophosphamide; Drug: vincristine sulfate; Drug: doxorubicin hydrochloride; Drug: dexamethasone; Drug: methotrexate; Drug: cytarabine; Drug: leucovorin calcium; Drug: methylprednisolone; Biological: rituximab; Other: laboratory biomarker analysis

Interventions

carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (carfilzomib and hyper-CVAD)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (carfilzomib and hyper-CVAD)

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Treatment (carfilzomib and hyper-CVAD)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria

Treatment (carfilzomib and hyper-CVAD)

dexamethasone DRUG

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (carfilzomib and hyper-CVAD)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (carfilzomib and hyper-CVAD)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Treatment (carfilzomib and hyper-CVAD)

leucovorin calcium DRUG

Given IV or PO

Also known as: CF, CFR, LV

Treatment (carfilzomib and hyper-CVAD)

methylprednisolone DRUG

Given IV

Also known as: Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort

Treatment (carfilzomib and hyper-CVAD)

rituximab BIOLOGICAL

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (carfilzomib and hyper-CVAD)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (carfilzomib and hyper-CVAD)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Newly diagnosed acute lymphoblastic leukemia/lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (3 if it is directly disease related and is expected to get better if the acute lymphoblastic leukemia/lymphoma \[ALL\] is under control)
• Left ventricular ejection fraction (LVEF) \> 40%
• Total bilirubin =\< 3 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.5 x upper limit of normal
• Creatinine clearance (CrCl) \>= 45 mL/minute within 7 days prior to enrollment either measured or calculated using a standard formula (eg, Cockcroft and Gault); in cases that creatinine clearance cannot be measured accurately, 24 hour urine can be used
• Disease free of other malignancies beside the ALL at the time of the study
• Male subjects must agree to practice contraception
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 24 hours prior to the initiation of the study and they must agree to ongoing pregnancy testing and to practice contraception

You may not qualify if:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females
• Active congestive heart failure (New York Heart Association \[NYHA\] class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention
• Unstable angina or myocardial infarction within 6 months prior to enrollment, NYHA class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities unless subject has a pacemaker
• Uncontrolled hypertension, uncontrolled pulmonary hypertension or uncontrolled diabetes within 14 days prior to enrollment
• Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 14 days of baseline
• Known history of allergy to Captisol®
• Known sero-positive for active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are sero-positive because of hepatitis B virus vaccine are eligible
• Breakpoint cluster region-Abelson positive (BCR-ABL +) patients will be excluded from the study

Sponsors & Collaborators

• Mehrdad Abedi, MD: lead
• Amgen: collaborator

Study Sites (1)

University of California Davis

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

carfilzomib; Cyclophosphamide; Vincristine; Doxorubicin; Dexamethasone; Calcium Dobesilate; Methotrexate; merphos; Cytarabine; Leucovorin; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Rituximab

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mehrdad Abedi

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2014
• First Posted: November 18, 2014
• Study Start: December 17, 2015
• Primary Completion: December 13, 2017
• Study Completion: January 11, 2018
• Last Updated: March 10, 2022

Record last verified: 2022-03

Locations

US (1)