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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00104975
Recruitment Status : Completed
First Posted : March 4, 2005
Last Update Posted : December 15, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Yale University

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Biological: alemtuzumab Biological: therapeutic allogeneic lymphocytes Drug: fludarabine phosphate Drug: melphalan Drug: tacrolimus Drug: thiotepa Procedure: peripheral blood stem cell transplantation Phase 1

Detailed Description:


  • 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  (Clinical Trial)
Estimated Enrollment : 20 participants
Primary Purpose: Treatment
Official Title: Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells
Study Start Date : February 2005
Actual Primary Completion Date : May 2008
Actual Study Completion Date : May 2008

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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.



  • 18 to 55

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified


  • Not specified


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


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


  • LVEF ≥ 45%


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


  • 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


Biologic therapy

  • Not specified


  • Not specified

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00104975

United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
Sponsors and Collaborators
Yale University
National Cancer Institute (NCI)
Study Chair: Erkut Bahceci, MD Yale University

Responsible Party: Yale University Identifier: NCT00104975     History of Changes
Other Study ID Numbers: CDR0000413698
First Posted: March 4, 2005    Key Record Dates
Last Update Posted: December 15, 2016
Last Verified: December 2016

Keywords provided by Yale University:
accelerated phase chronic myelogenous leukemia
recurrent adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
secondary myelodysplastic syndromes
chronic myelomonocytic leukemia
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
primary myelofibrosis
chronic neutrophilic leukemia
essential thrombocythemia
polycythemia vera
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage III adult Burkitt lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action