Phase III CDK in refractory C

• Conditions: chronic lymphocytic leukemia (CLL); MedDRA version: 14.1Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-005186-20-SE
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09-20
• Last Update Posted: 16 November 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 466

Inclusion Criteria

1. 18 years of age or older, or either sex, and of any race
2. Confirmed diagnosis of CLL, as defined by iwCLL criteria.
3. Have fludarabine or chemoimmunotherapy refractory disease defined as follows
• Fludarabine refractory defined as failing to respond to or relapsed within 6 months of completing fludarabine or another purine analog (e.g. pentostatin) alone or in combination regimens
or
• Chemoimmunotherapy refractory defined as failing to respond to chemoimmunotherapy or relapsed within 24 months of completing therapy with a combination of chemotherapy plus an anti-CD20 monoclonal antibody.
4. Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1, or 2
5. Adequate laboratory parameters to include:
• Creatinine = 2.0 mg/dL
• Bilirubin = 1.5 x ULN (unless secondary to Gilbert’s)
• AST and ALT = 2 x ULN, or if CLL involvement of the liver = 5 x ULN
• White blood cell count < 150 x 109/L
6. Women who are sexually active, including both female subjects and the female sexual partners of male subjects, of child-bearing potential must agree to use a medically accepted method of contraception prior to enrollment, while receiving protocol-specified medication, and for 6 months after stoppingdinaciclib or 12 months after stopping ofatumumab.

Note: Subjects who fulfill all the inclusion criteria are eligible for this trial but the protocol will require subjects with an increased risk of developing TLS on study treatment, defined as any one of the following
• White blood cell count > 50 x 109/L
• Bulky disease (any lymph node >5 cm by physical exam or CT scan)
• Splenomegaly (defined as spleen >18 cm by CT scan)
to be treated with a short term steroid based regimen prior to randomization

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 186

Exclusion Criteria

1. Symptomatic brain metastases or primary central nervous system malignancy.
2. Treatment with a CYP3A4 inhibitor or inducer within 1 week prior to randomization, or any chemotherapy or biologic therapy within 4 weeks prior to randomization.
3. Grade 2 or higher non-hematological toxicities from prior therapy. However, Grade 1 and Grade 2 persistent treatment-related neurotoxicity will be allowed.
4. Presence of any serious or uncontrolled infection at Screening (defined as infection requiring hospital admission and/or parenteral antibiotics).
5. Known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy.
6. Subjects with clinically active hepatitis B or C defined as disease that requires therapy
7. Allergy/sensitivity to study drug or its excipients.
8. Subjects who test positive for G6PD deficiency
9. Women who are breast-feeding, pregnant, or intend to become pregnant.
10. Prior allogeneic bone marrow transplant (auto HSCT is allowed if fully recovered).
11. Subjects with Richter's transformation.
12. Subjects with indeterminate deletion 17p status.
13. 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.
14. Any clinically significant condition or situation, other than the condition being studied that, in the opinion or the investigator, would interfere with the study evaluations or optimal participation in the study.
15. Any investigational drugs within 4 weeks prior to the start of treatment.
16. Concurrently receiving treatment in any other clinical study.
17. Previously treated with dinaciclib, ofatumumab or other CDK inhibitors.
18. Active autoimmune anemia or thrombocytopenia unless stable, defined as being responsive to corticosteroids or other standard therapy.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified