Non-Myeloablative Allogeneic Stem Cell Transplantation

November 2, 2011 updated by: M.D. Anderson Cancer Center

Allogeneic Stem Cell Transplantation With Rituximab Containing Nonablative Conditioning Regimen for Advanced/Recurrent Mantle Cell Lymphoma

  1. To determine the safety and efficacy of non-myeloablative allogeneic stem cell transplantation using rituximab, cyclophosphamide, fludarabine as a preparative regimen for patients with advanced or recurrent mantle cell lymphoma.
  2. To determine factors associated with response and durable remission in patients receiving rituximab, cyclophosphamide, and fludarabine in preparation for allogeneic stem cell transplantation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

MATCHED SIBLING TRANSPLANTS:

If you are found to be eligible to take part in this study, you will be admitted to the hospital to receive treatment. Two (2) chemotherapy drugs, fludarabine and cyclophosphamide, will be given each day for 3 days. The drugs will be given one at a time in a vein. Each treatment will take about 30 minutes. Fludarabine will be given first, and cyclophosphamide will be given 4 hours later. You will receive rituximab once a week for 4 weeks by vein over 4-8 hours. The first dose will starts one week before starting the chemotherapy.

Two days after finishing chemotherapy, you will receive a transplant of stem cells from a sibling. The stem cells will be infused into your vein. Seven days later, you will begin to receive a drug called granulocyte colony-stimulating factor (G-CSF). G-CSF helps the new stem cells do their normal work in the body;making new blood cells. You will receive G-CSF each day until your blood cell counts begin to recover to a certain level.

Sometimes the donor cells cause inflammation of the skin, liver and gut, and a reaction called graft-versus-host disease occurs. The drugs tacrolimus and methotrexate will be given to help decrease the risk of this. These drugs are also given through a vein before and after transplant . Tacrolimus will be infused two days before transplant and will continue to be given daily as a continuous infusion. Methotrexate will be given through the vein as a short infusion on Days 1, 3, and 6 after the transplant. Tacrolimus also comes in pill form, and you may switch to the pills when ready.

During your hospitalization, you will be examined daily, and blood (about 1 tablespoon) samples will be taken daily to evaluate your blood count levels, the function of your liver and kidneys, as well as electrolytes. This blood will also be used to measure tacrolimus levels and to look for any infections. You might be given blood transfusions if blood cell counts remain low.

MATCHED UNRELATED OR MISMATCHED SIBLING TRANSPLANTS:

Alemtuzumab is a drug that is designed to specifically attack some types of leukemia and lymphoma cells. In addition, it weakens the immune system, helping to prevent the rejection of donor marrow or stem cells.

TBI is designed to damage the DNA (the genetic material of cells) of cancer cells, which may kill the cancer cells.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

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.

If you are found to be eligible to take part in this study, you will be admitted to the hospital for treatment. Alemtuzumab will be injected into your vein over a period of 4 hours. This will be done 3 days in a row (Days 1 to 3). Drugs diphenhydramine (Benadryl), solumedrol and acetaminophen (Tylenol) will be given in to decrease the risk of or ease side effects before each dose of the alemtuzumab.

You will also receive fludarabine and cyclophosphamide once a day for 3 days. They will be given on the same days as alemtuzumab. Both drugs will be given through a catheter (plastic tube) that extends into the large chest vein. The catheter will be left in place throughout treatment on this study. Some participants, depending on their type of disease, will also receive rituximab. Rituximab will be given 8 days before the transplant and then once a week for a total of 4 doses.

After completion of chemotherapy, you will receive TBI, and later on the same day, blood stem cells from a donor will be given through the catheter. G-CSF, a growth factor that promotes the production of blood cells, will be injected under the skin once a day until your blood cell counts recover to a certain level.

Blood tests (about 2 tablespoons each) , urine tests, bone marrow aspirations, and x-rays will be done as needed to track the effects of the transplant. The blood tests will be drawn daily while in the hospital and then at least twice weekly as an outpatient for the first 100 days. The CT scans and bone marrow studies will be done at 1, 3, 6, and 12 months and then every 6 months for at least 3 years after transplant. You may also have transfusions of blood and platelets as needed.

IMMUNOMODULATION POST NONABLATIVE STEM CELL TRANSPLANTATION FOR PATIENTS WITH LYMPHOID MALIGNANCIES:

You will receive treatment as an outpatient. You will receive rituximab over 4 - 8 hours through a vein once a week for 4 weeks. You will also get a boost of cells from the same donor from whom you received the original transplant. These additional cells will be infused through the vein (over 30 - 60 minutes) between the second and the third dose of rituximab. The infusion may have to be done later if cells were not available as scheduled.

Sometimes the donor cells cause inflammation of the skin, liver and gut, and a reaction called graft-versus-host disease occurs. If this happens, the drug tacrolimus and methotrexate will be given to help control this reaction. These medications are usually given by pills on a daily basis.

A boost with a higher number of cells may be infused once a month for 3 months if there is no graft-versus-host disease and if disease remains.

During treatment, you will be examined as needed, and blood samples (1 tablespoon once or twice a week) will be taken for routine tests. You may need to receive blood transfusions during this study if your blood cell counts remain low.

******

About 40 patients will take part in this study, and all will be enrolled at M. D. Anderson.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients can be as old as 70 years.
  2. They must have a diagnosis of MCL, either (1) Recurrent, (2) Newly diagnosed (after cytoreduction with conventional chemotherapy) but with high-risk features (blastic or blastoid features, leukemic phase, or elevated B^2 microglobulin (> 3).
  3. Patients that have received prior conventional chemotherapy but have not achieved complete response (CR).
  4. Disease must be chemosensitive, (ie, patients must not have had a partial response to prior therapy).
  5. Patients whose disease failed to respond to a previous autologous transplantation may also be eligible.
  6. Patients must have a matched or 1 antigen mismatched sibling or unrelated donor.
  7. Point Scale (PS) </= 2.
  8. Inclusion criteria for Immunomodulation Post transplantation: Patients can be as old as 70 years. Patients must have a diagnosis of MCL or CLL with one of the following characteristics: 1. Patients who develop disease progression or do not experience a CR within 3 months post-allogeneic transplantation 2. Patients with a weak chimerism (any mixed chimerism of donor T cells in patients receiving Campath by day 90, and less than 20% for patients not receiving Campath) or a drop of 20% or more with an amount of donor cells present in the blood < 50% by PCR .
  9. Continued from Inclusion # 8: Patients must have the same donor of the original transplant willing to donate lymphocytes. 4. PS </ 2.

Exclusion Criteria:

  1. Past history of anaphylaxis following exposure to rat- or mouse-derived CDR-grafted humanized monoclonal antibodies.
  2. Less than 4 weeks since prior chemotherapy counted from first day of treatment regimen.
  3. Pregnancy or lactation.
  4. HIV or HTLV-I positivity.
  5. Serum creatinine concentration > 1.6 mg/dl or serum bilirubin > 2.0 mg/dl unless due to tumor
  6. pulmonary function test - carbon monoxide diffusing capacity < 40%
  7. cardiac ejection fraction < 40% of predicted levels (by multiple-gated acquisition or echocardiography).
  8. Severe concomitant medical or psychiatric illness.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Matched Sibling Transplant
Allogeneic Stem Cell Transplantation With Rituximab Containing Nonablative Conditioning Regimen: Cyclophosphamide 750 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine 30 mg/m^2 given intravenously on Days -5 and -3 before transplantation. Rituximab 375 mg/m^2 given intravenously on Days -13, -6 before transplantation and Days 16, 8 after transplantation.
Drug: Cyclophosphamide

Matched Donors:

750 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

Unrelated or Mismatched Donors:

1000 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine

30 mg/m^2 given intravenously on Days -5 and -3 before transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Other Names:
  • Fludara
  • Fludarabine phosphate
Drug: Rituximab

Matched Donors:

375 mg/m^2 given intravenously on Days -13, -6 before transplantation and Days 16, 8 after transplantation.

Unrelated/Mismatched Donors:

375 mg/m^2 given intravenously on Days -8, -1 before transplantation and Days 6, 13 after transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

For development of disease progression or no response, immunomanipulation with Rituximab 375 mg/m^2 given intravenously, then 1000 mg/m^2 given intravenously weekly for 3 weeks, and taper off Tacrolimus dose over 2 weeks.

DLI = Donor Lymphocyte Infusion/Immunomodulation Post Transplantation Immunomodulation for patients with lymphoid Malignancies:

375 mg/m^2 then 1000 mg/m^2 weekly x 3 if immunomanipulation is undertaken for persistent disease.

Other Names:
  • Rituxan
Procedure: Allogeneic Stem Cell Infusion
Infusion of stem cells.
Other Names:
  • ASCT
Experimental: Allo MUD & MM
Allo MUD & MM = Allogeneic Stem Cell Transplantation, Matched unrelated donor or mismatched sibling donor transplantations: Cyclophosphamide 1000 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine 30 mg/m^2 given intravenously on Days -5 and -3 before transplantation. Rituximab 375 mg/m^2 given intravenously on Days -8, -1 before transplantation and Days 6, 13 after transplantation. Alemtuzumab 15 mg per day given intravenously days 1 through 3 after transplantation.
Drug: Cyclophosphamide

Matched Donors:

750 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

Unrelated or Mismatched Donors:

1000 mg/m^2 given intravenously on Day -3, 4 hours after completion of Fludarabine.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Other Names:
  • Cytoxan
  • Neosar
Drug: Fludarabine

30 mg/m^2 given intravenously on Days -5 and -3 before transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Other Names:
  • Fludara
  • Fludarabine phosphate
Drug: Rituximab

Matched Donors:

375 mg/m^2 given intravenously on Days -13, -6 before transplantation and Days 16, 8 after transplantation.

Unrelated/Mismatched Donors:

375 mg/m^2 given intravenously on Days -8, -1 before transplantation and Days 6, 13 after transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

For development of disease progression or no response, immunomanipulation with Rituximab 375 mg/m^2 given intravenously, then 1000 mg/m^2 given intravenously weekly for 3 weeks, and taper off Tacrolimus dose over 2 weeks.

DLI = Donor Lymphocyte Infusion/Immunomodulation Post Transplantation Immunomodulation for patients with lymphoid Malignancies:

375 mg/m^2 then 1000 mg/m^2 weekly x 3 if immunomanipulation is undertaken for persistent disease.

Other Names:
  • Rituxan
Procedure: Allogeneic Stem Cell Infusion
Infusion of stem cells.
Other Names:
  • ASCT
Drug: Alemtuzumab

Unrelated/Mismatched Donors:

15 mg per day given intravenously days 1 through 3 after transplantation.

(Stem Cell Transplantation and Low Dose Total Body Irradiation = Day 0)

Other Names:
  • Campath
  • CAMPATH-1H

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Survival at 100 Days Post Transplant (Number of Surviving Participants)
Time Frame: 100 days post transplant
Overall Survival defined as the number of participants living at day 100 following non-myeloablative allogeneic stem cell transplantation using rituximab, cyclophosphamide, fludarabine as a preparative regimen for participants with advanced or recurrent mantle cell lymphoma.
100 days post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
M.D. Anderson Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Issa F. Khouri, MD, BS, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 6, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 2, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2004-0309

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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