Phase 1, Dose-Escalation, Pharmacodynamic Study of IV CNF1010 in ZAP-70 Positive CLL

This study has been terminated.
(Discontinuation of program)
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00319930
First received: April 27, 2006
Last updated: March 4, 2010
Last verified: March 2010
  Purpose

The purpose of the study is to evaluate the effects of increasing doses of CNF1010 on pharmacodynamic markers and hematological response.


Condition Intervention Phase
Chronic Lymphocytic Leukemia
Drug: CNF1010 (17-AAG)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Multi-Center, Open-Label, Dose-Escalation, Pharmacodynamic Study of Intravenously Administered CNF1010 (17-(Allylamino)-17-demethoxy-geldanamycin [17-AAG]) in Patients With ZAP-70 Positive B-Cell Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • The minimal biologically active dose (MBAD)
  • Safety and toxicity profile
  • Pharmacokinetics (PK)
  • Pharmacodynamics (PD)
  • Clinical and hematological response

Enrollment: 10
Study Start Date: May 2005
Study Completion Date: May 2007
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Diagnosis of B-cell CLL including

    • Lymphocytosis of >=5,000 monoclonal B-cells/microliter co-expressing >= one B-cell marker (CD19, CD20, or CD23) and CD5 in peripheral blood AND
    • <= 55% prolymphocytes AND
    • Bone marrow with >=30% mononuclear cells being lymphocytes
  2. ZAP-70 positive CLL
  3. Intermediate or High risk, poor prognosis CLL refractory to fludarabine-based therapy as defined by one of the following:

    • Disease progression following 2 cycles of fludarabine OR
    • Failure to achieve PR or CR after at least 2 cycles OR
    • No response to treatment or stable disease after at least 2 cycles of fludarabine OR
    • Disease progression after chemotherapy treatment after fludarabine-based therapy

    OR

    · CLL patients intolerant to fludarabine-based therapy. [Intolerance is defined as the development of any serious medical condition occurring after exposure to fludarabine that would restrict further use of the agent as treatment for the patient's CLL (i.e., autoimmune hemolytic anemia, myelosuppression, hypersensitivity)]

  4. Indication for treatment as defined by the NCI Working Group Guidelines
  5. Laboratory parameters as follows:

    • Hemoglobin >=10 g/dL (may be post-transfusion); platelet count >=50 x103/mm3
    • T. Bili <2 x ULN and ALT and AST <2 x ULN
    • Creatinine <=2 x ULN
  6. ECOG Performance Score <=2
  7. For patients of child-producing potential, use of effective contraceptive methods during the study and for 1 month following treatment

Key Exclusion Criteria:

  1. Pregnant or nursing women
  2. Class III or IV cardiac disease defined by the New York Heart Association Functional Classification and/or left ventricular ejection fraction <40%
  3. History of prior radiation that potentially included the heart in the field.
  4. History of myocardial infarction or active ischemic heart disease within 6 months of study entry
  5. History of arrhythmia (including atrial fibrillation, multifocal premature ventricular contractions, ventricular bigeminy or trigeminy, ventricular tachycardia or a requirement for antiarrhythmics (including digoxin)
  6. Baseline QTc >=450 msec for men and >= 470 msec for women in the absence of correctable electrolyte imbalance
  7. Poorly controlled angina
  8. Congenital long QT syndrome or first-degree relative with unexplained sudden death <40 years of age
  9. Presence of left bundle branch block
  10. Treatment with chemotherapy, monoclonal antibody or radiotherapy within 28 days of study entry
  11. Severe or debilitating pulmonary disease
  12. Participation in any investigational drug study within 28 days prior to CNF1010 administration. (Patient must have recovered from all acute effects of previously administered investigational agents)
  13. Presence of active malignancy with the exception of basal cell carcinoma
  14. Active symptomatic fungal, bacterial and/or viral infection including active HIV or viral (A, B or C) hepatitis
  15. Known allergy to soy
  16. Requirement for concomitant therapy with drugs that alter metabolism by cytochrome P450 3A4 except low-dose warfarin for implanted device patency
  17. Requirement for concomitant therapy with drugs that prolong or may prolong QTc interval
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319930

Locations
United States, Florida
Ocoee, Florida, United States, 34761
United States, New York
Albany, New York, United States, 12208
United States, Ohio
Dayton, Ohio, United States, 45409
United States, South Carolina
Greenville, South Carolina, United States, 29605
United States, Texas
Tyler, Texas, United States, 75702
United States, Virginia
Norfolk, Virginia, United States, 85258
Sponsors and Collaborators
Biogen Idec
  More Information

No publications provided

Responsible Party: Study MD, Biogen Idec
ClinicalTrials.gov Identifier: NCT00319930     History of Changes
Other Study ID Numbers: CNF1010-CLL-05001, 110CL101
Study First Received: April 27, 2006
Last Updated: March 4, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen Idec:
Chronic lymphocytic leukemia
CLL
ZAP-70
Hsp90 inhibitor

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 10, 2014