Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma

January 22, 2024 updated by: Washington University School of Medicine

Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

This is a research study testing a new approach to treating high-risk non-Hodgkin's lymphoma consisting of an autologous hematopoietic (blood) stem cell transplant (using a patient's own hematopoietic cells) followed by a non-myeloablative allogeneic transplantation (transplant from another individual).

The investigators hypothesize that the addition of the second non-myeloablative transplant will improve the chances for long-term control of lymphoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The approach to recurrent or primary refractory non-Hodgkin's lymphoma has been to treat patients with second-line chemotherapy (usually 2-3 courses) for the purposes of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells have been mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease.

In a group of 17 patients with transformed lymphoma who received autologous transplants at Stanford University, the median EFS and OS were 1.48 and 2.7 years respectively with a 7-year survival of only 20%. In comparison, patients with chemosensitive follicular lymphoma who received the same regimen also had a poor median EFS of 1.3 years, but the median survival was 6.7 years. The outcomes for patients with chemotherapy-resistant relapsed NHL is also poor with EFS in the range of 20% in many studies of autologous transplantation.

These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that we have taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. In addition, there are limited reports of using an autologous/allogeneic approach for lymphoma patients using non-myeloablative allogeneic transplants. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide, cytarabine and melphalan with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

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
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University

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

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Age 18 to 70 years.
  • Histologically proven non-Hodgkin's lymphoma

  • High risk disease including at least one of the following:

    • Relapsed or refractory disease
    • Transformed lymphoma
    • Aggressive T-cell lymphoma
    • Failure to achieve completed remission (CR) following Auto SCT
    • Less than a 20% chance of event-free survival from autologous transplant determined by the treating physician and the Principal Investigator
  • ECOG performance status < or = 2

  • Underwent Autologous SCT 60-120 days prior to registration including:

    • BEAM conditioning (BCNU: 300 mg/m2 IV day -7, Etoposide: 100 mg/m2 IV BID days -6,-5,-4,-3, Cytarabine: 100 mg/m2 IV BID days -6,-5,-4,-3, Melphalan: 140 mg/m2 IV day -2)
    • Minimum of 2 x 106 CD34+ cells/kg infused

  • Full hematologic recovery following Auto HCT including:

    • Absolute neutrophil count (ANC) >1000 µl
    • Platelet count of ≥50,000 µl independent of transfusion for >7 days
  • Available matched related or unrelated donor. Selected donor must be a complete match or have only a single antigen mismatch.
  • Women of child-bearing potential and sexually active males must use an accepted and effective method of birth control.
  • Bone marrow comprising of < 10% lymphoma on most recent biopsy/aspiration (within 9 months of Allo transplant; may have been performed prior to autologous transplant).
  • Serum bilirubin < or = 2 x the institutional ULN

  • Serum creatinine < or = 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min by the following formula

    • Estimated Creatinine Clearance = (140 age)X WT(kg) X 0.85 if female 72X serum creatinine(mg/dl).
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria

  • Prior autologous or allogeneic hematopoietic cell transplantation (other than autologous SCT 60-120 days prior to registration)
  • Prior radioimmunotherapy
  • Known or suspected progressive disease following autologous SCT
  • Additional treatment for NHL administered from time of autologous SCT through registration
  • Pregnant or breast-feeding women (due to the known birth defects association with the treatments used in this study)
  • Human immunodeficiency virus (HIV)-positive (the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population.)
  • Any prior malignancy is allowed except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years.
  • Active infection requiring oral or intravenous antibiotics.

Inclusion of Women and Minorities

-Both men and women and members of all races and ethnic groups are eligible for this trial.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allogeneic Transplant
  • TLI - 80 cGy on days -14, -11, -10, -9, -8, -7, -4, -3, -2, -1
  • Anti-thymocyte globulin (ATG) 1.5 mg/kg on days -11, -10, -8, -7
  • Solumedrol - 1 mg/kg on days -11, -10, -9, -8, -7
  • Tacrolimus - beginning on day -3 with starting dose of 0.3 mg/kg PO BID. Will be continued per institutional guidelines.
  • Stem cell infusion - day 0
  • Mycophenolate mofetil (MMF) - beginning on day 0 with dose of 15 mg/kg PO (5-10 hours after transplant)
Drug: Tacrolimus
Other Names:
  • Prograf
  • Protopic
  • FK-506
  • Advagraf
Drug: Mycophenolate mofetil
Other Names:
  • CellCept
  • Myfortic
  • MMF
Procedure: Stem cell infusion
Procedure: TLI
Drug: Anti-thymocyte globulin
Other Names:
  • ATG
  • Thymoglobulin
  • Atgam
Drug: Solumedrol
Other Names:
  • Medrol
  • Solu-Medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the event free survival
Time Frame: Up to 10 years from transplant
Up to 10 years from transplant
Determine the toxicities
Time Frame: Day 100
Day 100

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism.
Time Frame: Day 56, Day 100, Day 180, and Day 365
Day 56, Day 100, Day 180, and Day 365
To evaluate the incidence and extent of acute and chronic GVHD.
Time Frame: Up to 10 years
Up to 10 years
To evaluate the overall and non-relapse mortality rate.
Time Frame: Up to 10 years
Up to 10 years
Incidence of chemotherapy-associated pneumonitis
Time Frame: Day 100
Day 100

Collaborators and Investigators

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

Sponsor

Washington University School of Medicine

Investigators

  • Principal Investigator: Keith Stockerl-Goldstein, MD, Washington University School of Medicine

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.

General Publications

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 (Actual)

May 5, 2009

Primary Completion (Estimated)

June 1, 2028

Study Completion (Estimated)

June 1, 2028

Study Registration Dates

First Submitted

April 15, 2009

First Submitted That Met QC Criteria

April 16, 2009

First Posted (Estimated)

April 17, 2009

Study Record Updates

Last Update Posted (Estimated)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-0042 / 201101864

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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