Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation and Leukemias

NCT00472849 | Completed Phase 1 Results

• 1 other identifier: 2006-1026
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of fludarabine and cytarabine that can be given in combination with oxaliplatin and rituximab in the treatment of chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, or Richter's transformation. Once the highest tolerable dose for this drug combination is found, the next goal of the study will be to find out if this combination therapy is effective in shrinking or slowing the growth of these diseases.

Conditions

Richter's Transformation; Leukemia

Keywords

OFAR 2; Oxaliplatin; Fludarabine; Cytarabine; Ara-C; Rituximab; Richter's Transformation; Prolymphocytic Leukemia; B-Cell Chronic Lymphocytic Leukemia; Leukemia; CLL

Outcome Measures

Primary Outcomes (1)

• Maximum Total Tolerated Dose (MTD) of Daily Combination Fludarabine 30 mg/m^2 and Cytarabine 500 mg/m^2 Among 3 Dose Levels (Dose Level 1: 2 Days, Dose Level 2: 3 Days or Dose Level 3: 4 Days)

  Maximum dose levels for Phase I determined among three possible dose levels of Fludarabine and Cytarabine in combination with fixed doses of Oxaliplatin and Rituximab. Fludarabine and Cytarabine Dose Level 1: Days 2-3 (2 Days); Dose Level 2: Days 2-4 (3 Days); and Dose 3: Days 2-5 (4 Days). MTD is dose level at which less than 2/3 or 2/6 participants experience dose limiting toxicities (DLTs). The number of days of fludarabine and cytarabine administration increased simultaneously. Participants received a subsequent cycle of treatment with 1 additional day of fludarabine and cytarabine treatment no less than 4 weeks from the initiation of the previous cycle if no drug-related grade 3 or 4 non-hematologic life-threatening adverse events, and drug-related non-hematologic toxicity resolved to baseline or \< grade 2. A maximum of 6 cycles were administered.

  Up to 36 weeks (6 cycles each 4-6 weeks)

Secondary Outcomes (1)

• Overall Response: Number of Participants With Complete Remission, Nodular Partial Remission, and Partial Remission

  Up to 36 weeks (6 cycles each 4-6 weeks)

Study Arms (2)

OFAR (Phase I)

EXPERIMENTAL

Oxaliplatin starting dose 30 mg/m\^2/day over 2 hours on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily intravenous (IV) over 30 minutes on days 2-3, 2-4, or 2-5 until maximum tolerated dose reached. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose (MTD) reached. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.

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

OFAR MTD (Phase II)

EXPERIMENTAL

Oxaliplatin 25 mg/m\^2 IV per day MTD on days 1-4 before Fludarabine. Fludarabine 30 mg/m\^2 daily IV over 30 minutes on days 2-4. Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after fludarabine dose started, on days 2-4. Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses). Pegfilgrastim 6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy.

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

Interventions

Oxaliplatin DRUG

Oxaliplatin 30 mg/m\^2/day, over approximately 2 hours, before fludarabine is started, on days 1-4.

OFAR (Phase I); OFAR MTD (Phase II)

Fludarabine DRUG

Fludarabine 30 mg/m\^2 daily IV, over approximately 30 minutes, on days 2-3, 2-4, or 2-5 until maximum tolerated dose is reached.

Also known as: Fludara

OFAR (Phase I); OFAR MTD (Phase II)

Cytarabine DRUG

Cytarabine 500 mg/m\^2 daily IV, 2-hour infusion starting 4 hours after first fludarabine dose is started, on days 2-3, 2-4, or 2-5, until maximum tolerated dose is reached.

Also known as: Cytosar, Ara-C

OFAR (Phase I); OFAR MTD (Phase II)

Rituximab DRUG

Rituximab 375 mg/m\^2 IV on day 3, course 1 (on day 1, subsequent courses).

Also known as: Rituxan

OFAR (Phase I); OFAR MTD (Phase II)

Pegfilgrastim DRUG

6 mg subcutaneously once per chemotherapy cycle, approximately 24 hours after last dose of chemotherapy

Also known as: Neulasta

OFAR (Phase I); OFAR MTD (Phase II)

Eligibility Criteria

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

You may qualify if:

• All patients with histologically or cytologically confirmed Richter's transformation, prolymphocytic leukemia, aggressive, or relapsed/refractory B-cell chronic lymphocytic leukemia are eligible for this protocol.
• 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 \<= 2 mg/dL or creatinine clearance \> 50 mL/min). Patients with renal dysfunction due to organ infiltration by disease may be eligible after discussion with the principal investigator (PI) and consideration of appropriate dose adjustments.
• Patients must have adequate hepatic function (bilirubin \<= 2 mg/dl; aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) \< 2.5 \* the upper limit of normal (ULN) for the reference lab unless due to leukemia or congenital hemolytic disorder \[for bilirubin\]). Patients with hepatic dysfunction due to organ infiltration by disease may be eligible after discussion with the PI and consideration of appropriate dose adjustments.
• 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.
• Patients must have platelet counts \> 20,000, unless lower counts are 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 (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas MD Anderson Cancer Center's Official Website

MeSH Terms

Conditions

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

Interventions

Oxaliplatin; fludarabine; fludarabine phosphate; Cytarabine; Rituximab; pegfilgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; 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 G. Wierda, MD, PhD, BS / Associate Professor
• Organization: The University of Texas MD Anderson Cancer Center

eharriso@mdanderson.org

713-745-0428

Study Officials

• William G. Wierda, M.D., PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

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: May 11, 2007
• First Posted: May 14, 2007
• Study Start: May 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: November 26, 2013
• Results First Posted: November 26, 2013

Record last verified: 2013-11

Locations

US (1)