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Chemotherapy Followed by Allogeneic Stem Cell Transplantation in Treating Children With Hematologic Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), July 2009
First Received: July 11, 2001   Last Updated: July 7, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00020592
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, 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 cyclosporine after the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying how well combination chemothearpy, low-dose chemotherapy, and allogeneic stem cell transplant work in treating children with hematologic cancers.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: filgrastim
Biological: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: fludarabine phosphate
Drug: methotrexate
Drug: prednisone
Drug: vincristine sulfate
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: Pilot Study Of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation For Pediatric Hematopoietic Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Antitumor activity [ Designated as safety issue: No ]
  • Biologic activity [ Designated as safety issue: No ]

Estimated Enrollment: 56
Study Start Date: March 2001
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   4 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Hodgkin's lymphoma or non-Hodgkin's lymphoma, meeting 1 of the following criteria:

      • Refractory to primary treatment regimen
      • Refractory to or relapse after salvage regimen
    • Acute myelogenous leukemia

      • Prior bone marrow relapse in second or later complete remission (CR)
    • Acute lymphoblastic leukemia, meeting 1 of the following criteria:

      • Prior bone marrow relapse in second or later CR
      • First CR and Philadelphia chromosome (Ph) positive or prior induction failure
    • Acute hybrid leukemia including mixed lineage, biphenotypic, and undifferentiated, meeting 1 of the following criteria:

      • Prior bone marrow relapse in second or later CR
      • First CR and Ph positive or prior induction failure
    • Myelodysplastic syndromes

      • Less than 10% blasts in bone marrow and blood
      • Refractory anemia (RA) and RA with ringed sideroblasts not eligible
      • Must be Fanconi's anemia negative
    • Chronic myelogenous leukemia, meeting 1 of the following criteria:

      • Chronic phase
      • Accelerated phase with less than 10% blasts in bone marrow and blood
    • Juvenile myelomonocytic leukemia

      • Less than 10% blasts in bone marrow and blood
  • No active CNS malignancy

    • No tumor mass by CT scan for patients with lymphoma
    • No CNS 2 or 3 classification for patients with leukemia
    • No leptomeningeal disease
    • Prior CNS involvement allowed if no current evidence of CNS malignancy
  • Donor criteria:

    • 5 or 6 antigen HLA-matched first-degree related donor

      • Single HLA-A or B locus mismatch allowed
    • Weight more than 15 kilograms

PATIENT CHARACTERISTICS:

Age:

  • 4 to 21

Performance status:

  • ECOG 0-2

Life expectancy:

  • More than 3 months

Hematopoietic:

  • See Disease Characteristics

Hepatic:

  • Bilirubin < 2.0 mg/dL
  • ALT/AST ≤ 2.5 times upper limit of normal (elevations due to malignancy may be allowed at the discretion of the principal investigator)
  • No active hepatitis B
  • No active hepatitis C

Renal:

  • Creatinine normal for age OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular:

  • LVEF ≥ 45% by MUGA OR
  • Shortening fraction ≥ 28% by echocardiogram

Pulmonary:

  • DLCO ≥ 50% of predicted

Other:

  • No high risk of inability to comply with protocol
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior autologous bone marrow transplantation allowed
  • At least 100 days since prior allogeneic bone marrow transplantation with no ongoing active graft-vs-host disease

Chemotherapy:

  • Prior chemotherapy to achieve criteria for Disease Characteristics allowed
  • Concurrent intrathecal chemotherapy for CNS leukemia or CNS lymphoma allowed

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Concurrent radiotherapy for testicular leukemia, CNS leukemia, or CNS lymphoma allowed

Surgery:

  • Not specified

Other:

  • Other concurrent therapy or prophylaxis for testicular leukemia or CNS lymphoma allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00020592

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
Sponsors and Collaborators
Investigators
Study Chair: Alan S. Wayne, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
Publications:
Wayne A, Fowler D, Fry T, et al.: Immune depletion prior to non-myeloablative (NM) allogeneic hematopoietic stem cell transplantation (alloSCT) results in rapid full donor engraftment in pediatric patients with malignancy. [Abstract] Blood 102 (11 Pt 1): A-3607, 2003.

Responsible Party: NCI - Pediatric Oncology Branch ( Alan S. Wayne )
Study ID Numbers: CDR0000068621, NCI-01-C-0125F
Study First Received: July 11, 2001
Last Updated: July 7, 2009
ClinicalTrials.gov Identifier: NCT00020592     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent childhood lymphoblastic lymphoma
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent/refractory childhood Hodgkin lymphoma
acute undifferentiated leukemia
secondary myelodysplastic syndromes
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
juvenile myelomonocytic leukemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
chronic myelomonocytic leukemia
childhood myelodysplastic syndromes

Study placed in the following topic categories:
Anti-Inflammatory Agents
Anti-Infective Agents
Chronic Myelomonocytic Leukemia
Prednisone
Cyclosporine
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Cyclosporins
Preleukemia
Acute Myelocytic Leukemia
Neoplasm Metastasis
Methotrexate
Etoposide
Hodgkin Disease
Myelodysplastic Myeloproliferative Disease
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Antineoplastic Agents, Hormonal
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myeloproliferative Disorders
Juvenile Myelomonocytic Leukemia
Vincristine
Leukemia, Myeloid
Glucocorticoids
Doxorubicin
Folic Acid

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormones
Cyclosporins
Preleukemia
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Vincristine
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Doxorubicin
Neoplasms
Fludarabine
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 11, 2009