Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer or Aplastic Anemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00053989
First received: February 5, 2003
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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 Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Aplastic Anemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Safety [ Time Frame: Weekly while on study ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: Weekly while on study ] [ Designated as safety issue: Yes ]
  • Clinical response [ Time Frame: Weekly until day +100 ] [ Designated as safety issue: No ]
  • Overall outcome [ Time Frame: Yearly until progression ] [ Designated as safety issue: No ]
  • Incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism [ Time Frame: Day 30-40, day 60-70 and day 100-120 ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: January 2002
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: anti-thymocyte globulin
    iv
    Biological: graft-versus-tumor induction therapy
    iv
    Biological: sargramostim
    iv
    Biological: therapeutic allogeneic lymphocytes
    iv
    Drug: cyclophosphamide
    injection
    Drug: fludarabine phosphate
    iv
    Other Name: FLUDARA
    Drug: methylprednisolone
    oral
    Drug: mycophenolate mofetil
    oral
    Drug: tacrolimus
    oral
    Procedure: allogeneic bone marrow transplantation
    iv
    Procedure: peripheral blood stem cell transplantation
    iv
    Procedure: umbilical cord blood transplantation
    iv
Detailed Description:

OBJECTIVES:

  • 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.

OUTLINE:

  • 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.

NOTE: *This regimen is tapered from days 30-60 if donor chimerism of T-cells is 100%. MMF is then stopped and tacrolimus is tapered by 25% every 10 days and discontinued by day 90 if no GVHD develops.

  • 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.

  Eligibility

Ages Eligible for Study:   5 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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.

PATIENT CHARACTERISTICS:

Age

  • 5 to 75 (if related donor transplantation)
  • 5 to 60 (if unrelated donor transplantation)

Performance status

  • Karnofsky > 50%

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • 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

Renal

  • Creatinine clearance greater than 40 mL/min

Cardiovascular

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

Pulmonary

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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • At least 6 months since prior autologous bone marrow transplantation (BMT)
  • At least 12 months since prior allogeneic BMT

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • At least 4 weeks since prior radiotherapy

Surgery

  • At least 4 weeks since prior surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053989

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Philip L. McCarthy, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00053989     History of Changes
Other Study ID Numbers: CDR0000269673, RP01-05
Study First Received: February 5, 2003
Last Updated: October 8, 2013
Health Authority: United States: Food and Drug Administration

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:
Anemia
Anemia, Aplastic
Neoplasms
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Precancerous Conditions
Antilymphocyte Serum
Cyclophosphamide
Mycophenolate mofetil
Fludarabine phosphate

ClinicalTrials.gov processed this record on August 28, 2014