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B-cell Chronic Lymphocytic LeukemiaPhase 1NCT00612612

Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

A Phase 1 study testing obatoclax mesylate, fludarabine phosphate and rituximab in people with B-cell Chronic Lymphocytic Leukemia and Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Obatoclax may stop the growth of chronic lymphocytic leukemia by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
obatoclax mesylate, fludarabine phosphate and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
Jan 2008to Jul 2013
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Histologically or cytologically confirmed diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) or prolymphocytic leukemia (PLL) arising from CLL
  • No de novo PLL
  • Malignant B cells must co-express CD5 with CD19 or CD20
  • Patients who lack CD23 expression on their leukemia cells may not have t(11;14) or cyclin D1 overexpression, to rule out mantle cell lymphoma
  • Must have documented lymphocytosis of > 5,000/uL
  • Must require therapy based on any of the following criteria:
Show all 28Show fewer
  • Massive or progressive splenomegaly and/or lymphadenopathy
  • Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelet count < 100,000/uL)
  • Presence of weight loss > 10% over the preceding 6-month period
  • NCI grade 2 or 3 fatigue
  • Fevers > 100.5 F or night sweats for > 2 weeks without evidence of infection
  • Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 6 months
  • Must have received at least one prior therapy for B-CLL
  • No known brain metastases
  • ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
  • Total bilirubin normal (unless due to Gilbert syndrome or compensated hemolysis)
  • Life expectancy > 3 months
  • Creatinine normal
  • Fertile patients must use effective contraception
  • Not pregnant or nursing
  • Negative pregnancy test
  • Any number of prior therapies allowed
  • At least 1 year since prior fludarabine phosphate-rituximab combination therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No chemotherapy or radiotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • No other concurrent investigational agents
  • AST and ALT < 2.5 times upper limit of normal
  • Recovered from all prior therapy

Who cannot join

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to obatoclax mesylate or other agents used in study
  • Active Coombs' positive autoimmune hemolytic anemia
  • Chronic active hepatitis B patients if not on appropriate antiviral therapy (e.g., lamivudine, adefovir)
  • Other neurological disorders or dysfunction or a history of seizure disorder
  • Uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
Show all 10Show fewer
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia including QTc > 450 msec
  • Psychiatric illness/social situations that would limit compliance with study requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase 1 Study of Obatoclax Mesylate (GX15-070MS) in Combination With Fludarabine-Based Chemoimmunotherapy in Previously Treated Patients With B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Obatoclax may stop the growth of chronic lymphocytic leukemia by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving obatoclax together with fludarabine and rituximab may kill more cancer cells. This phase I trial is studying the side effects and best dose of obatoclax when given together with fludarabine and rituximab in treating patients with B-cell chronic lymphocytic leukemia.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the maximum tolerated dose of obatoclax mesylate in combination with fludarabine phosphate-rituximab (FR) in patients with relapsed chronic lymphocytic leukemia.

SECONDARY OBJECTIVES:

  1. To evaluate toxicity of obatoclax mesylate in combination with FR in this patient population.

II. To determine objective response rate and progression-free survival of obatoclax mesylate in combination with FR.

III. To correlate levels of anti-apoptotic Bcl-2 family members with drug response.

IV. To determine whether apoptosis is induced via the mitochondrial pathway in response to obatoclax mesylate and further enhanced by FR.

OUTLINE: This is a dose-escalation study of obatoclax mesylate.

Patients receive obatoclax mesylate IV over 3 hours on days 1 and 3, fludarabine IV over 20-30 minutes on days 1-5, and rituximab IV over 4 hours on day 1 (days 1 and 3 of course 1 only). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo peripheral blood collection for correlative studies. Samples are analyzed for expression of pro- and anti-apoptotic Bcl-2 family members by western blot; apoptosis induction by measurement of lymphocyte count, Annexin V staining, and Caspase and PARP cleavage; activated Bax by immunoprecipitation; and Bax promoter polymorphism by PCR amplification and direct sequencing.

After completion of study therapy, patients are followed every 6 months.

Being tested
obatoclax mesylate, fludarabine phosphate, rituximab, laboratory biomarker analysis
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Leukemia, Prolymphocytic

What participants receive

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

  • obatoclax mesylateDrug

    Also called GX15-070MS

    Given IV

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • laboratory biomarker analysisOther

    Correlative study

Study groups in NCT00612612
Study groupRoleWhat they receive
Treatment (obatoclax mesylate, fludarabine, rituximab)ExperimentalPatients receive obatoclax mesylate IV over 3 hours on days 1 and 3, fludarabine IV over 20-30 minutes on days 1-5, and rituximab IV over 4 hours on day 1 (days 1 and 3 of course 1 only). Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo peripheral blood collection for correlative studies. Samples are analyzed for expression of pro- and anti-apoptotic Bcl-2 family members by western blot; apoptosis induction by measurement of lymphocyte count, Annexin V staining, and Caspase and PARP cleavage; activated Bax by immunoprecipitation; and Bax promoter polymorphism by PCR amplification and direct sequencing.
Receives: Drug: obatoclax mesylate; Drug: fludarabine phosphate; Biological: rituximab; Other: laboratory biomarker analysis

What is being measured

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

  1. Maximum tolerated dose of obatoclax mesylate

    DLT will be defined as any non-hematologic toxicity of grade 3 or greater severity (excluding asymptomatic grade 3 laboratory abnormalities that are not life-threatening and respond to treatment; grade 3 fatigue; grade 3 nausea, vomiting or diarrhea occurring without optimal prophylaxis; or expected grade 3 rituximab infusion reactions). Any grade 4 non-hematological toxicity, as well as any irreversible grade 2 cardiac, renal or neurologic toxicities, will be considered dose-limiting. Grading of non-hematologic toxicities will be according to NCI CTC version 3.0.

    Measured: 28 days

Secondary outcomes (1)

  1. Response evaluated using the Revised National Cancer Institute-sponsored Working Group Guidelines

    Described using descriptive statistics. Ninety-five percent confidence intervals will be calculated where appropriate.

    Measured: Up to 2 years

Timeline

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

  1. First posted11 Feb 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionJul 2013

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00612612
Sponsor's protocol ID
NCI-2009-00254
Other IDs
NCI-2009-00254, CDR0000582311, 07-100, 07-100, 7945, U01CA062490
Status last verified
Sep 2013
First submitted
8 Feb 2008
Last updated
30 Sep 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing obatoclax mesylate, fludarabine phosphate and rituximab in people with B-cell Chronic Lymphocytic Leukemia and 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 28 inclusion and 10 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: stopped early, as of the sponsor's last update on 30 Sep 2013. 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 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.

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

Are results available for this study?

The study was stopped early. Results are not available in the source record.

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 obatoclax mesylate (time frame: 28 days). 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 NCT00612612.

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 30 Sep 2013.

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