Non-Myeloablative Allogeneic Stem Cell Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00525876
First received: September 4, 2007
Last updated: November 2, 2011
Last verified: November 2011
  Purpose
  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.

Condition Intervention
Lymphoma
Drug: Cyclophosphamide
Drug: Fludarabine
Drug: Rituximab
Drug: Alemtuzumab
Procedure: Allogeneic Stem Cell Infusion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation With Rituximab Containing Nonablative Conditioning Regimen for Advanced/Recurrent Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Overall Survival at 100 Days Post Transplant (Number of Surviving Participants) [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
    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.


Enrollment: 49
Study Start Date: January 2005
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Fludarabine phosphate
  • Fludara
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 Name: Rituxan
Procedure: Allogeneic Stem Cell Infusion
Infusion of stem cells.
Other Name: 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:
  • Fludarabine phosphate
  • Fludara
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 Name: Rituxan
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-1H
  • Campath
Procedure: Allogeneic Stem Cell Infusion
Infusion of stem cells.
Other Name: ASCT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00525876

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Issa F. Khouri, MD, BS M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00525876     History of Changes
Other Study ID Numbers: 2004-0309
Study First Received: September 4, 2007
Results First Received: November 2, 2011
Last Updated: November 2, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Mantle Cell Lymphoma
Lymphoma
Allogeneic Stem Cell Transplant
Rituximab
Cyclophosphamide
Neosar
Cytoxan
Fludarabine
Fludara
Fludarabine phosphate
Rituxan
Alemtuzumab
CAMPATH-1H
Campath
Total Body Irradiation
TBI

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Fludarabine monophosphate
Campath 1G
Rituximab
Fludarabine
Alemtuzumab
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on April 15, 2014