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

NCT01515176 | Completed Phase 1 Results DMC

• 12 other identifiers: NCI-2012-00101OSU-11120OSU11120CDR0000721353OSU 111209031N01CM00070N01CM62207P30CA016058P50CA140158U01CA076576UM1CA186712
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (3)

• 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.

  Day 56

• 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.

  Up to day 56

• 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.

  Up to 28 weeks

Secondary Outcomes (4)

• Complete Response Rate

  Up to 28 weeks

• Overall Survival

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

• Progression Free Survival

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

• Time to Treatment Failure

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

Study Arms (1)

Treatment (ofatumumab, dinaciclib)

EXPERIMENTAL

Patients 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.

Drug: Dinaciclib; Other: Laboratory Biomarker Analysis; Biological: Ofatumumab; Other: Pharmacological Study

Interventions

Dinaciclib DRUG

Given IV

Also known as: CDK Inhibitor SCH 727965, MK-7965, SCH 727965

Treatment (ofatumumab, dinaciclib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ofatumumab, dinaciclib)

Ofatumumab BIOLOGICAL

Given IV

Also known as: Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2

Treatment (ofatumumab, dinaciclib)

Pharmacological Study OTHER

Correlative studies

Treatment (ofatumumab, dinaciclib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic

Interventions

dinaciclib; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jeffrey Jones, MD
• Organization: The Ohio State University Comprehensive Cancer Center

Jeffrey.Jones@osumc.edu

614-293-3507

Study Officials

• Kerry Rogers, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: January 23, 2012
• Study Start: January 1, 2012
• Primary Completion: March 4, 2015
• Study Completion: July 19, 2016
• Last Updated: March 15, 2018
• Results First Posted: March 15, 2018

Record last verified: 2018-02

Locations

US (1)