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Contiguous Stage II Adult Lymphoblastic LymphomaPhase 1NCT02293109

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

A Phase 1 study testing carfilzomib, cyclophosphamide and vincristine sulfate in people with Contiguous Stage II Adult Lymphoblastic Lymphoma and Noncontiguous Stage II Adult Lymphoblastic Lymphoma, run by Mehrdad Abedi, MD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 64 years
What is being tested?
carfilzomib, cyclophosphamide and vincristine sulfate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
17 Dec 2015to 11 Jan 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: Phase I Study of Escalating Doses of Carfilzomib With Hyper-CVAD in Patients With Newly Diagnosed Acute Lymphoblastic Leukemia/Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Safety and tolerability of administering carfilzomib in combination with hyper-CVAD chemotherapy.

II. Recommended dose of carfilzomib in combination with hyper-CVAD chemotherapy for the future phase II trial.

SECONDARY OBJECTIVES:

  1. Rate of remission after 2nd and 4th cycles. II. Incidence of minimal residual disease by flow cytometry at 4th cycle.

OUTLINE: This is a dose escalation study of carfilzomib.

Patients receive carfilzomib intravenously (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 orally (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 cluster of differentiation (CD)20 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.

After completion of study treatment, patients are followed up for 28 days.

Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • carfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • vincristine sulfateDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria

    Given IV

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, DM

    Given PO

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV or PO

  • methylprednisoloneDrug

    Also called Depo-Medrol, Medrol, MePRDL, Solu-Medrol

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02293109
Study groupRoleWhat they receive
Treatment (carfilzomib and hyper-CVAD)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 56 days (after second course)

Secondary outcomes (3)

  1. Rate of remission

    All responses will be reported. Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.

    Measured: Up to 56 days (after second course)

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

    MRD will be defined an aberrant expression of at least 2 antigens in comparison with the known patterns of antigen expression by normal maturing CD19 positive B-cells. A distinct cluster of at least 20 cells showing altered antigen expression will be characterized as an aberrant cell population.

    Measured: Up to 56 days (after second course)

  3. Rate of MRD in bone marrow aspirate samples

    MRD will be defined an aberrant expression of at least 2 antigens in comparison with the known patterns of antigen expression by normal maturing CD19 positive B-cells. A distinct cluster of at least 20 cells showing altered antigen expression will be characterized as an aberrant cell population.

    Measured: Up to 112 days (after 4th course)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2014 (estimated)
  2. Study start17 Dec 2015
  3. Primary completion13 Dec 2017
  4. Study completion11 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02293109
Sponsor's protocol ID
660258
Other IDs
UCDCC#246, UCDCC#246, NCI-2014-02245
Status last verified
Mar 2022
First submitted
13 Nov 2014
Last updated
10 Mar 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing carfilzomib, cyclophosphamide and vincristine sulfate in people with Contiguous Stage II Adult Lymphoblastic Lymphoma and Noncontiguous Stage II Adult Lymphoblastic Lymphoma, run by Mehrdad Abedi, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: Up to 56 days (after second course)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02293109.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2022.

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