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NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders

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ClinicalTrials.gov Identifier: NCT00053989
Recruitment Status : Completed
First Posted : February 6, 2003
Results First Posted : February 10, 2020
Last Update Posted : February 10, 2020
Information provided by (Responsible Party):
Roswell Park Cancer Institute

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 (donor lymphocyte infusion) 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 immunosuppressive therapy before or after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.

Condition or disease Intervention/treatment Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Fanconi Anemia Aplastic Anemia Biological: anti-thymocyte globulin Biological: graft-versus-tumor induction therapy Biological: sargramostim Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methylprednisolone Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation Phase 2

Detailed Description:


  • Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
  • Determine clinical response and overall outcome of patients treated with this regimen.
  • Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.


  • Preparative regimen:

    • Matched related and unrelated donor transplantation:

      • Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
    • Cord blood transplantation:

      • Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
  • Graft-vs-host disease (GVHD) prophylaxis:

    • Matched related and unrelated donor transplantation:

      • Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.
    • Cord blood transplantation:

      • Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
  • Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  • Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.

Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Non-Myeloablative Allogeneic Hematopoietic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Disorders
Actual Study Start Date : January 29, 2002
Actual Primary Completion Date : July 19, 2018
Actual Study Completion Date : July 19, 2018

Arm Intervention/treatment
Experimental: All patients
All patients enrolled on study
Biological: anti-thymocyte globulin

Biological: graft-versus-tumor induction therapy

Biological: sargramostim

Biological: therapeutic allogeneic lymphocytes

Drug: cyclophosphamide

Drug: fludarabine phosphate
Other Name: FLUDARA

Drug: methylprednisolone

Drug: mycophenolate mofetil

Drug: tacrolimus

Procedure: allogeneic bone marrow transplantation

Procedure: peripheral blood stem cell transplantation

Procedure: umbilical cord blood transplantation

Primary Outcome Measures :
  1. Day 100 TRM [ Time Frame: from start or conditioning (day -6 or -5) through day +100 after HSC infusion ]
    treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0

  2. Day 100 Best Response [ Time Frame: from start of conditioning on day -6 or -5 through day +100 after HSC infusion ]
    Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol

Secondary Outcome Measures :
  1. PFS [ Time Frame: 1 year ]
    Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion

  2. OS [ Time Frame: 1 year ]
    Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion

  3. Acute GvHD [ Time Frame: Day +100 ]
    overall grade II-IV acute GvHD

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of aplastic anemia

    • Severe disease
    • Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin OR
  • Histologically confirmed hematologic malignancy including the following:

    • Acute leukemia

      • Any of the following types:

        • Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes
        • Secondary AML
        • AML with high-risk cytogenetic abnormalities
        • Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities
      • Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR
      • In first remission at high risk of relapse
    • Chronic myelogenous leukemia

      • Chronic phase meeting at least 1 of the following criteria:

        • Failed imatinib mesylate
        • Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week
        • Unable to tolerate interferon
      • Accelerated phase (blasts less than 20%)
    • Myeloproliferative and myelodysplastic syndromes

      • Myelofibrosis (after splenectomy)
      • Refractory anemia
      • Refractory anemia with excess blasts
      • Chronic myelomonocytic leukemia
    • Lymphoproliferative disease

      • Chronic lymphocytic leukemia

        • Symptomatic disease after first-line chemotherapy
      • Low-grade non-Hodgkin's lymphoma (recurrent or persistent)

        • Symptomatic disease after first-line chemotherapy
      • Multiple myeloma

        • Progressive disease after autologous stem cell transplantation
      • Waldenstrom's macroglobulinemia

        • Failed 1 standard regimen
    • Non-Hodgkin's lymphoma meeting the following criteria:

      • Intermediate or high grade
      • Controlled and chemosensitive disease
      • First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse
    • Hodgkin's lymphoma

      • Relapsed and chemosensitive disease
  • Not eligible for standard myeloablative allogeneic stem cell transplantation
  • Availability of any of the following donor types:

    • Related donor matched at 5 or 6 HLA antigens (A, B, DR)
    • Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci

      • Single antigen mismatch at C allowed
    • Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted
  • No uncontrolled CNS disease (for hematologic malignancies) 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.



  • 4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation)
  • 4 to 60 (if unrelated cord blood transplantation)

Performance status

  • Karnofsky > 50%

Life expectancy

  • Not specified


  • Not specified


  • Bilirubin less than 3 times normal
  • Alkaline phosphatase less than 3 times normal
  • AST/ALT less than 3 times normal
  • No Child's class B or C liver failure


  • Creatinine clearance greater than 40 mL/min


  • Cardiac ventricular ejection fraction at least 35% by MUGA
  • No cardiovascular disease


  • DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV antibody negative
  • No uncontrolled diabetes mellitus
  • No active serious infection
  • No other disease that would preclude study therapy
  • No other concurrent malignancy except non-melanoma skin cancer
  • No concurrent serious psychiatric illness


Biologic therapy

  • See Disease Characteristics
  • patients may have received a prior autologous blood or marrow transplantation (BMT)
  • At least 6 months since prior allogeneic BMT


  • See Disease Characteristics
  • At least 2 weeks since prior chemotherapy, radiation or surgery

Endocrine therapy

  • Not specified


  • At least 2 weeks since prior radiotherapy


  • At least 2 weeks since prior surgery

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 ClinicalTrials.gov identifier (NCT number): NCT00053989

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United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
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Principal Investigator: Philip L. McCarthy, MD Roswell Park Cancer Institute
  Study Documents (Full-Text)

Documents provided by Roswell Park Cancer Institute:
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Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00053989    
Other Study ID Numbers: CDR0000269673
First Posted: February 6, 2003    Key Record Dates
Results First Posted: February 10, 2020
Last Update Posted: February 10, 2020
Last Verified: December 2019
Keywords provided by Roswell Park Cancer Institute:
accelerated phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
primary myelofibrosis
de novo myelodysplastic syndromes
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory anemia with excess blasts
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Waldenstrom macroglobulinemia
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
adult acute myeloid leukemia in remission
secondary acute myeloid leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
childhood acute lymphoblastic leukemia in remission
adult acute lymphoblastic leukemia in remission
noncontiguous stage II adult lymphoblastic lymphoma
refractory multiple myeloma
refractory anemia
refractory chronic lymphocytic leukemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
grade 1 follicular lymphoma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Anemia, Aplastic
Myeloproliferative Disorders
Fanconi Anemia
Myelodysplastic-Myeloproliferative Diseases
Pathologic Processes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions