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Chronic Lymphocytic LeukemiaPhase 1/2NCT01515176

Ofatumumab and Dinaciclib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or B-Cell Prolymphocytic Leukemia

A Phase 1/2 study testing Dinaciclib, Laboratory Biomarker Analysis and Ofatumumab in people with Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, run by National Cancer Institute (NCI) 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/II trial studies the side effects and the best dose of ofatumumab and dinaciclib and to see how well they work in treating patients with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-cell prolymphocytic leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Dinaciclib, Laboratory Biomarker Analysis and Ofatumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
Jan 2012to 19 Jul 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologically confirmed B-cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) or a B-cell prolymphocytic leukemia (B-PLL) according to 2008 World Health Organization (WHO) diagnostic criteria
  • Patients must meet one or more of the following modified indications for treatment as described in the 2008 International Workshop on chronic lymphocytic leukemia (CLL) (IWCLL) guidelines for the diagnosis and treatment of CLL:
  • Progressive disease or marked splenomegaly and/or lymphadenopathy or disease requiring de-bulking for future allogeneic transplantation
  • Anemia (hemoglobin < 11 mg/dL) or thrombocytopenia (platelets < 100,000/μL)
  • Unexplained weight loss exceeding 10% of body weight over the preceding 6 months
  • Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 fatigue
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  • Fevers > 100.5 º F or night sweats for greater than 2 weeks without evidence of infection
  • Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of less than 6 months
  • Need for cytoreduction prior to allogeneic stem cell transplant
  • Patients must have received at least one prior therapy that includes either fludarabine or equivalent nucleoside analogue, or an alternative regimen if there was a contraindication (i.e. autoimmune hemolytic anemia) or patient elected not to receive fludarabine
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy >= 12 weeks
  • Absolute neutrophil count >= 1,000/μL in absence of bone marrow involvement
  • Platelets >= 30,000/μL in absence of bone marrow involvement
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) unless secondary to Gilbert's
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal (ULN) unless due to infiltration of the liver
  • Creatinine =< 2.0 mg/dL OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients(Cockcroft-Gault estimated)
  • Patients with a history of current/previous infection with hepatitis B virus will be eligible if receiving appropriate antiviral prophylaxis
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; corticosteroids alone will not be considered prior therapy, but must be discontinued at least 24 hours prior to the first day of therapy unless continued for indications other than the primary malignancy
  • Patients who are receiving any other investigational agents
  • Patients who have received prior treatment with dinaciclib will not be eligible; patients previously treated with ofatumumab will be eligible as long as their disease responded to previous treatment (defined as achieving at least stable disease by consensus criteria) and did not subsequently progress < 3 months from completing treatment
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition as dinaciclib
  • History of anaphylactic reaction to rituximab or other anti-cluster of differentiation (CD)20 monoclonal antibody
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  • Because dinaciclib is metabolized by the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) liver enzyme, the eligibility of patients taking medications that are potent inducers or inhibitors of that enzyme will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications; any identified agent needs to be stopped at least 2 weeks prior to study registration; use of aprepitant will be permitted, however, based on drug-drug interaction study performed by the manufacturer showing no effect on dinaciclib pharmacokinetics (PK)
  • Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency are excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and/or breast-feeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with dinaciclib
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject is considered by his or her physician to have a 2 year survival expectation
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL

This phase I/II trial studies the side effects and the best dose of ofatumumab and dinaciclib and to see how well they work in treating patients with relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-cell prolymphocytic leukemia. Monoclonal antibodies, such as ofatumumab, can find cancer cells and help kill them. Dinaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ofatumumab together with dinaciclib may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib (phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and B-cell prolymphocytic leukemia (B-PLL).

II. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in CLL/SLL/B-PLL.

III. To determine the overall response rate associated with this treatment as assessed by consensus response criteria. (Phase II)

SECONDARY OBJECTIVES:

  1. To estimate progression-free survival (PFS) after combination treatment with ofatumumab and dinaciclib.

II. To characterize the pharmacokinetics of dinaciclib when given in combination with ofatumumab.

III. To correlate pharmacokinetic features of dinaciclib with response, toxicity (particularly tumor lysis syndrome), and pharmacodynamic endpoints.

IV. To perform detailed baseline and serial pharmacodynamic studies of combination therapy with ofatumumab and dinaciclib and correlate these with response to therapy.

  1. To correlate baseline disease-risk parameters (i.e., zeta-chain-associated protein kinase [ZAP]-70 expression, interphase cytogenetics, immunoglobulin heavy chain variable region [IgVH] mutational analysis, and other clinical prognostic factors) with response to therapy.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive ofatumumab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.

Being tested
Dinaciclib, Laboratory Biomarker Analysis, Ofatumumab, Pharmacological Study
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Prolymphocytic

What participants receive

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

  • DinaciclibDrug

    Also called CDK Inhibitor SCH 727965, MK-7965, SCH 727965

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • OfatumumabBiological

    Also called Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01515176
Study groupRoleWhat they receive
Treatment (ofatumumab, dinaciclib)ExperimentalPatients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2 hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment repeats every 28 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dinaciclib; Other: Laboratory Biomarker Analysis; Biological: Ofatumumab; Other: Pharmacological Study

What is being measured

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

  1. Maximum-tolerated Dose of Dinaciclib When Given in Combination With Ofatumumab, Defined as a Dose Level Where at Most One of 6 Evaluable Patients Has a Dose Limiting Toxicity (Phase Ia)

    Graded according to the National Cancer Institute (NCI) CTCAE version (v)4.0. Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.

    Measured: Day 56

  2. Number of Patients With Dose-limiting Toxicity Incidents Graded According to the NCI CTCAE v4.0 (Phase I)

    Hematologic dose-limiting toxicity measures will be assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTCAE version 4 standard toxicity grading. Non-hematologic dose-limiting toxicities such as dyspnea and renal will be evaluated via the ordinal CTCAE standard toxicity grading only.

    Measured: Up to day 56

  3. Percentage of Patients Who Achieve an Overall Response, Defined as Achieving a Complete Response, an Unconfirmed Complete Response (SLL Only), or a Partial Response (Phase II)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 28 weeks

Secondary outcomes (4)

  1. Complete Response Rate

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions

    Measured: Up to 28 weeks

  2. Overall Survival

    Distributions will be explored and assessed using the methods of Kaplan and Meier.

    Measured: Time from study entry to death due to any cause, assessed up to 5 years

  3. Progression Free Survival

    95% confidence intervals will be constructed using the methods of Duffy and Santner with the assumption that these rates are binomially distributed. Distributions will be explored and assessed using the methods of Kaplan and Meier.

    Measured: Time from study entry to documentation of disease progression and/or death, assessed up to 5 years

  4. Time to Treatment Failure

    Distributions will be explored and assessed using the methods of Kaplan and Meier.

    Measured: Time from study entry to the date patients end treatment, up to 28 weeks

Timeline

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

  1. First posted23 Jan 2012 (estimated)
  2. Study startJan 2012
  3. Primary completion4 Mar 2015
  4. Study completion19 Jul 2016

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01515176
Sponsor's protocol ID
NCI-2012-00101
Other IDs
NCI-2012-00101, OSU-11120, OSU11120, CDR0000721353, OSU 11120, 9031, N01CM00070, N01CM62207
Status last verified
Feb 2018
First submitted
16 Jan 2012
Last updated
15 Mar 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dinaciclib, Laboratory Biomarker Analysis and Ofatumumab in people with Chronic Lymphocytic Leukemia and Prolymphocytic Leukemia, run by National Cancer Institute (NCI) 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 20 inclusion and 12 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 15 Mar 2018. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Dinaciclib When Given in Combination With Ofatumumab, Defined as a Dose Level Where at Most One of 6 Evaluable Patients Has a Dose Limiting Toxicity (Phase Ia) (time frame: Day 56). The study lists 3 primary outcomes in all. 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 NCT01515176.

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 15 Mar 2018.

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