Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

December 13, 2016 updated by: Yale University

Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells

RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of donor lymphocytes when given after alemtuzumab and combination chemotherapy in treating patients who are undergoing donor stem cell transplant for hematologic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the feasibility and efficacy of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies.
  • Determine the toxicity of this regimen in these patients.
  • Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells, administered after allogeneic PBSCT, in these patients.

OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted donor T cells.

  • T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order to selectively deplete T cells from the donor PBMCs.
  • Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5, fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day -4, and thiotepa IV on days -3 to -2.
  • Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1.
  • Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic PBSC transplantation on day 0.
  • LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2 immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on approximately day 28.

Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated, selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting-toxicity.

After completion of study treatment, patients are followed weekly for 100 days post-transplantation and then periodically for survival.

PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

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
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8028
        • Yale 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

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:

    • Chronic myelogenous leukemia

      • Accelerated phase or blast phase

    • Acute myeloid leukemia, meeting any of the following criteria:

      • In second or subsequent remission
      • In primary induction failure
      • In partial remission
      • In resistant relapse

    • Chronic lymphocytic leukemia

      • In Richter's transformation

    • High-grade non-Hodgkin's lymphoma

      • Refractory to standard treatment

    • Myeloproliferative disorders

      • Undergoing transformation to terminal stages

    • Myelodysplastic syndromes (MDS), including any of the following:

      • Refractory anemia with excess blasts
      • Transformation to acute leukemia
      • MDS secondary to chemotherapy

  • Partially-matched related family donor available

    • One HLA haplotype match
  • No HLA-matched (10/10 or 9/10) sibling donor or unrelated donor available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

  • 18 to 55

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • SGOT and SGPT < 3 times upper limit of normal (ULN)
  • No active or persistent viral hepatitis

Renal

  • Creatinine < 2.0 mg/dL* OR
  • Creatinine clearance > 60 mL/min* NOTE: *Unless due to malignancy

Cardiovascular

  • LVEF ≥ 45%

Pulmonary

  • DLCO ≥ 60% of predicted* (corrected for hemoglobin) NOTE: *Unless patient is given clearance by a pulmonary consultation

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 2 years after completion of study treatment
  • HIV negative
  • Human T cell lymphotrophic virus type 1 negative
  • No serious co-morbid medical condition
  • No other medical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

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

Collaborators and Investigators

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

Sponsor

Yale University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Erkut Bahceci, MD, Yale University

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

February 1, 2005

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

March 3, 2005

First Submitted That Met QC Criteria

March 3, 2005

First Posted (Estimate)

March 4, 2005

Study Record Updates

Last Update Posted (Estimate)

December 15, 2016

Last Update Submitted That Met QC Criteria

December 13, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000413698
  • YALE-25971
  • NCI-6765

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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