A Phase I/IIa Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies
Protocol # 07-C-0006
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the treatment plan?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Why is this trial important?
This study aims to determine the highest dose of ABT-263 that can safely be given to patients with lymphoma while evaluating the safety and effectiveness of ABT-263 in treating patients with lymphoma that has recurred (come back) or is refractory (did not respond to prior treatment). In addition, we hope to determine how the body absorbs and handles ABT-263. Finally, we hope to find biomarkers (substances in the blood or tissue that may indicate the effects or progress of the disease and activity of ABT-263).
Who is eligible for this trial? (PDQ)
Phase I
- Histologically confirmed B- and T-cell lymphoid malignancies
- Refractory or progressive disease
- At least one prior chemotherapy regimen
- No prior allogeneic or autologous stem cell transplant
- No prior or concurrent diagnosis of the following:
- Post-transplant lymphoproliferative disease
- Burkitt’s-like lymphoma
- Lymphoblastic lymphoma/leukemia
- Multiple myeloma
- HIV-associated lymphoma
Phase II
- One of the following histologically confirmed lymphoid malignancies:
- Arm A
- Follicular lymphoma
- Arm B
- Mantle cell lymphoma
- Peripheral T-cell lymphoma
- Cutaneous T-cell lymphoma including mycosis fungoides and Sezary syndrome
- Other indolent B-cell lymphoma such as marginal zone lymphoma
- Arm C
- Diffuse large B-cell lymphoma
- Measurable disease
- Archived diagnostic tissue available for assessment of Bcl-2 family protein expression
Phase I and Phase II
- ≥ 18 years of age
- No HIV
- Subjects receiving SSRI must be on a stable dose for 21 days before starting study drug
- Males and females of reproductive potential must agree to use an effective contraceptive method
- ECOG Performance Status 0–1
- Adequate bone marrow, renal, and hepatic function
- No history of cancer-related CNS disease, lymphoid or non-lymphoid
- No underlying, predisposing condition of bleeding or current signs of bleeding
- No anticoagulation therapy or any drugs that affect platelet function with the exception of low-dose anticoagulation medications that are used to maintain the patency of a central venous catheter
What types of drugs or therapies are being used?
ABT-263 is a novel small molecule Bcl-2 family protein inhibitor that binds with high affinity to multiple anti-apoptotic Bcl-2 family proteins. ABT-263 displays potent mechanism-based cytotoxicity against human tumor cell lines derived from small cell lung carcinomas and lymphoid malignancies. ABT-263 exhibits potent single agent activity against 10 of 22 cell lines consisting of multiple leukemia and lymphoma types spanning both B-cell and T-cell malignancies.
What is the treatment plan? (PDQ)
This is a multicenter, phase I, dose escalation study followed by an open-label, phase II study (phase II pending approval).
Phase I
- Patients receive oral ABT-263 once daily starting with a 7-day lead-in period at a lower dose, then begin continuous daily dosing
- Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity
- Blood samples are acquired periodically during study treatment; samples are examined for pharmacokinetics and proteomics
- After completion of study treatment, patients are followed at 21 and 30 days
Phase II
- Patients receive oral ABT-263 at the maximum tolerated dose determined in phase I
What is the frequency and duration of the visits?
Patients take ABT-263 by mouth daily for 14 days followed by 7 days off the drug in 21-day treatment cycles. On cycle 1, the patient will be required to stay in the local area for days 1 through 5, 8, 14, and 15. On cycle 2, days 1 through 3, 8, 14, and 21. On subsequent cycles, the patient will be required to stay in the local area days 1 through 3, 14, and 21. The patient will be seen in clinic at NIH prior to starting each cycle. Patients will be treated as outpatients and only admitted to the inpatient unit as need per PI approval.
What are the costs?
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Who is the Principal Investigator?
Dr. Wyndham H. Wilson received his B.A. and M.S. degrees in biology from Stanford University in 1975. In 1981, he received his Ph.D. in neurobiology and M.D. from Stanford, completing his residency training in internal medicine at Stanford in 1984. From 1984 to 1987, he was a clinical associate in the Medicine Branch, NCI, where he completed a fellowship in medical oncology. Dr. Wilson was special assistant to the director, Division of Cancer Treatment, NCI, from 1988 to 1995. In 1995, he joined the former Medicine Branch as a senior oncologist.
Where is this trial taking place?
NIH Clinical Center
National Institutes of Health
NCI Metabolism Branch
10 Center Drive
Bethesda, Maryland 20892
Who are the contacts for this trial?
Wyndham H. Wilson, M.D., Ph.D.
Principal Investigator
Phone: 301-435-2415
wilsonw@mail.nih.gov
Referrals:
Peggy Shovlin, R.N., B.S.N.
Research Nurse
Phone: 301-594-6597
mshovlin@mail.nih.gov
Where can additional information be found?
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