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Richter's TransformationPhase 1/2NCT00472849

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

A Phase 1/2 study testing Oxaliplatin, Fludarabine and Cytarabine in people with Richter's Transformation and Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Richter's Transformation, Leukemia
What is being tested?
Oxaliplatin, Fludarabine and Cytarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
92 participants
Where
1 siteUnited States
Study dates
May 2007to Feb 2012
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia, Aggressive, Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

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.

Read the detailed description

Cytarabine is designed to insert itself into DNA (the genetic material of cells) and stop the DNA from repairing itself.

Oxaliplatin is designed to kill cancer cells by damaging their DNA.

Fludarabine is designed to make cancer cells less able to repair damaged DNA. This may increase the likelihood of the cells dying.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

During the Phase I portion of the study, researchers will be testing different doses of the study drug combination. Oxaliplatin and rituximab will be given at the same dose level. However, fludarabine and cytarabine will be given daily for 2 days to the first 3 participants, daily for 3 days to the next 3 participants, and daily for 4 days to the next 3 participants. Although the plan is to treat 3, up to 6 participants may be treated in each of these groups.

If participants who receive the fludarabine and cytarabine for 2 or 3 days do not experience intolerable side effects, after the second cycle they may receive the next higher dose (an additional day of fludarabine and cytarabine) for the following cycles.

Once the highest tolerated dose of fludarabine and cytarabine given in combination with oxaliplatin and rituximab is found, the next group of participants entering the study will take part in the Phase II portion of the study. Participants in the Phase II portion will receive the study drugs at the highest tolerated dose found in the Phase I portion of the study. The goal of this part of the study is to look at how effective the drug combination is in treating patients with Richter's syndrome, prolymphocytic leukemia, and aggressive, relapsed, or refractory CLL. The same dose levels for all 4 drugs will be used throughout the Phase II portion of the study, unless intolerable side effects occur. In that case, the dose may be lowered or the treatment may be stopped.

  • Each cycle will be repeated every 4-6 weeks, depending on your blood counts and your medical condition.
  • You will receive oxaliplatin through a needle in your vein over about 2 hours on Days 1-4 of every 28-day study "cycle."
  • You will receive rituximab by vein over about 4-6 hours on Day 3 of the first cycle and on Day 1 on every cycle after that.
  • Starting on Day 2, you will receive fludarabine by vein over about 30 minutes and cytarabine by vein over about 2 hours for 2, 3, or 4 days.
  • On Day 6, you will receive peg-filgrastim subcutaneously (through a needle just under your skin) to help increase your white blood cell count.
  • On the days that you receive the study drugs, you will also be given fluids (such as saline) by vein to keep you from becoming dehydrated. If you receive the treatment as an outpatient, this means that the visit may take up to 8 hours.
  • Additional drugs will be given before each dose of rituximab to lower the risk of side effects. If side effects do occur, rituximab may have to be stopped until the side effects go away, at which point the drug may be restarted. This may make your time in the outpatient area longer.
  • The first study cycle will be given at MD Anderson. Depending on your response, up to 5 more cycles will be given either at MD Anderson or at home with your regular doctor.
  • Every 1-2 weeks, blood samples (about 1 teaspoon each) will be drawn for routine tests.
  • At the end of every cycle, you will have a physical exam and blood (about 1 teaspoon) will be drawn to determine whether you should receive another cycle.
  • You will have a bone marrow biopsy/aspirate at the end of the 3rd and 6th cycles. The biopsy at the end of cycle 3 will be used to determine if you are responding to treatment and will determine whether you should continue to receive the study drug combination.

You may remain on study for up to 6 cycles. You will be taken off-study early if the disease gets worse or intolerable side effects occur.

Once you are no longer receiving treatment, you will have an end-of-treatment visit. At this visit, you will have a physical exam and blood (about 1 teaspoon) will be drawn for routine tests.

If you achieve remission, after your last cycle is complete, you will have blood drawn (about 2 teaspoons each) every 3 months for routine tests. These tests will continue for as long as you are in remission.

This is an investigational study. Fludarabine, cytarabine, oxaliplatin, and rituximab are all FDA approved and commercially available. The use of these drugs together is investigational. Up to 102 patients will take part in this multicenter study. Up to 90 will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.

Keywords
OFAR 2, Oxaliplatin, Fludarabine, Cytarabine, Ara-C, Rituximab, Richter's Transformation, Prolymphocytic Leukemia, B-Cell Chronic Lymphocytic Leukemia, Leukemia, CLL
Medical subject headings
Leukemia, Leukemia, Prolymphocytic, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • OxaliplatinDrug

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

  • FludarabineDrug

    Also called Fludara

    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.

  • CytarabineDrug

    Also called Cytosar, Ara-C

    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.

  • RituximabDrug

    Also called Rituxan

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

  • PegfilgrastimDrug

    Also called Neulasta

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

Study groups in NCT00472849
Study groupRoleWhat they receive
OFAR (Phase I)ExperimentalOxaliplatin 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.
Receives: Drug: Oxaliplatin; Drug: Fludarabine; Drug: Cytarabine; Drug: Rituximab; Drug: Pegfilgrastim
OFAR MTD (Phase II)ExperimentalOxaliplatin 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.
Receives: Drug: Oxaliplatin; Drug: Fludarabine; Drug: Cytarabine; Drug: Rituximab; Drug: Pegfilgrastim

What is being measured

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

  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.

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

Secondary outcomes (1)

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

    Overall Response includes Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) in high-risk, previously untreated participants with Chronic Lymphocytic Leukemia treated with CFAR using National Cancer Institute - Working Group response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)>1,500/uL, Platelets >100,000uL, Hemoglobin (untransfused) >11.0g/dL, Lymphocytes <4,000/uL and Bone Marrow Aspirate biopsy <30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes >/= 50% decrease,Liver/spleen >/= 50% decrease, symptoms not applicable, PMN >1,500/uL or >50% improvement from baseline, Platelets 100,000uL or >/=50% decrease improvement from baseline, Hemoglobin (untransfused) >11.0g/dL or >50% improvement from baseline, Lymphocytes >50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with <30% lymphocytes with residual disease on biopsy.

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

Timeline

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

  1. First posted14 May 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionFeb 2012
  4. Study completionFeb 2012

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
92 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00472849
Sponsor's protocol ID
2006-1026
Status last verified
Nov 2013
First submitted
11 May 2007
Last updated
26 Nov 2013
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Oxaliplatin, Fludarabine and Cytarabine in people with Richter's Transformation and Leukemia, run by M.D. Anderson Cancer Center 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 8 inclusion and 5 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: finished, as of the sponsor's last update on 26 Nov 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 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) (time frame: Up to 36 weeks (6 cycles each 4-6 weeks)). 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 NCT00472849.

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 26 Nov 2013.

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