Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Richter's Syndrome, Refractory CLL and PLL

NCT00452374 | Completed Phase 1 Results

• 1 other identifier: 2004-0373
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objectives:

1. 1.Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of oxaliplatin in combination with fludarabine, Ara-C and rituximab in patients with Richter's transformation, prolymphocytic leukemia (PLL), or refractory/relapsed B-cell chronic lymphocytic leukemia (CLL).
2. 2.Assess the complete response (CR) and partial response (PR) rate to combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
3. 3.Determine the safety and toxicity profile of combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
4. 4.Determine the duration of response, failure-free survival, and overall survival.
5. 5.Determine the incidence of infections (bacterial, fungal, and viral) in patients with Richter's transformation, prolymphocytic leukemia or refractory/relapsed B-cell CLL treated with rituximab, oxaliplatin, fludarabine and Ara-C; monitor immune parameters such as T cell counts and immunoglobulin levels; and monitor Epstein-Barr virus (EBV) status.
6. 6.Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation, cross-link formation and excision deoxyribonucleic acid (DNA) responses. Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C.

Conditions

Leukemia

Keywords

B-cell chronic lymphocytic leukemia; Chronic Lymphocytic Leukemia; CLL; Prolymphocytic Leukemia; PLL; Richter's Transformation; High-grade non-Hodgkin's lymphoma; Hodgkin's disease; Acute leukemia; Small lymphocytic lymphoma; Oxaliplatin; Eloxatin; Fludarabine; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride; Rituximab; Rituxan

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) Oxaliplatin

  MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale.

  From treatment onset to end of each cycle of treatment (every 21 days)

Secondary Outcomes (1)

• Number of Participants With a Complete Response or Partial Response

  Evaluation every 3 cycles of treatment (28 days per cycle), approximately 90 days

Study Arms (1)

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

EXPERIMENTAL

Starting dose oxaliplatin 17.5mg/m\^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m\^2 IV and Cytarabine 1 g/m\^2 IV for two days, + Rituximab 375 mg/m\^2 IV on Day 3, Cycle 1 then Day 1 following cycles.

Drug: Cytarabine; Drug: Fludarabine; Drug: Oxaliplatin; Drug: Rituximab

Interventions

Cytarabine DRUG

1 g/m\^2 given IV for two days (Days 2 and 3).

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

Fludarabine DRUG

30 mg/m\^2 given IV for two days (Days 2 and 3).

Also known as: Fludara, Fludarabine Phosphate

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

Oxaliplatin DRUG

Starting dose of 17.5 mg/m\^2 IV for 4 days (Days 1 through 4).

Also known as: Eloxatin

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

Rituximab DRUG

375 mg/m\^2 IV on Day 3 of the first cycle over 4-6 hours and on Day 1 on every cycle following.

Also known as: Rituxan

Oxaliplatin, Fludarabine, Cytarabine + Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed Richter's transformation, fludarabine-refractory chronic lymphocytic leukemia or prolymphocytic leukemia.
• Patients must be 18 years of age or older.
• Patients must have a performance status of 0-2 (Zubrod scale).
• Patients must have adequate renal function (serum creatinine below or equal to 2mg/dL or creatinine clearance greater than 30mL/min), unless renal dysfunction is considered due to organ infiltration by disease.
• Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times the upper limit of normal (ULN) for the reference lab unless considered due to leukemia or congenital hemolytic disorder (for bilirubin).
• Female patients of childbearing potential (including those \<1 year post-menopausal) and male patients must agree to use contraception.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
• Patients must have platelet counts greater or equal to 20,000, unless due to disease involvement, or autoimmune disorders.

You may not qualify if:

• Untreated or uncontrolled life-threatening infection.
• Oxaliplatin, fludarabine, cytarabine or rituximab intolerance.
• Pregnancy or lactation.
• Chemotherapy and/or radiation therapy within 4 weeks.
• Medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Sanofi: collaborator

Study Sites (2)

University of California-San Diego

La Jolla, California, 92093, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Hodgkin Disease

Interventions

Cytarabine; fludarabine; fludarabine phosphate; Oxaliplatin; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: William Wierda, M.D./Associate Professor
• Organization: The University of Texas M. D. Anderson Cancer Center

eharriso@mdanderson.org

713-745-0428

Study Officials

• William G. Wierda, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2007
• First Posted: March 27, 2007
• Study Start: November 1, 2004
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: November 2, 2011
• Results First Posted: August 29, 2011

Record last verified: 2011-10

Locations

US (2)