NCT00612612

Brief 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 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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2008

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

February 8, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

February 11, 2008

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2013

Completed
Last Updated

September 30, 2013

Status Verified

September 1, 2013

Enrollment Period

5.5 years

First QC Date

February 8, 2008

Last Update Submit

September 27, 2013

Conditions

B-cell Chronic Lymphocytic LeukemiaLeukemiaProlymphocytic LeukemiaRefractory Chronic Lymphocytic LeukemiaStage I Chronic Lymphocytic LeukemiaStage II Chronic Lymphocytic LeukemiaStage III Chronic Lymphocytic LeukemiaStage IV Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (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.

    28 days

Secondary Outcomes (1)

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

    Up to 2 years

Study Arms (1)

Treatment (obatoclax mesylate, fludarabine, rituximab)

EXPERIMENTAL

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.

Drug: obatoclax mesylateDrug: fludarabine phosphateBiological: rituximabOther: laboratory biomarker analysis

Interventions

obatoclax mesylateDRUG

Given IV

Also known as: GX15-070MS
Treatment (obatoclax mesylate, fludarabine, rituximab)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (obatoclax mesylate, fludarabine, rituximab)
rituximabBIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Treatment (obatoclax mesylate, fludarabine, rituximab)
laboratory biomarker analysisOTHER

Correlative study

Treatment (obatoclax mesylate, fludarabine, rituximab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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%
  • +13 more criteria

You may not qualify if:

  • 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
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia including QTc \> 450 msec
  • Psychiatric illness/social situations that would limit compliance with study requirements

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellLeukemiaLeukemia, Prolymphocytic

Interventions

obatoclaxfludarabine phosphateRituximab

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Jennifer Brown

    Dana-Farber Cancer Institute

    PRINCIPAL INVESTIGATOR

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

February 8, 2008

First Posted

February 11, 2008

Study Start

January 1, 2008

Primary Completion

July 1, 2013

Last Updated

September 30, 2013

Record last verified: 2013-09

Locations

US(1)