T-Cell Depleted Bone Marrow and G-CSF Stimulated Peripheral Stem Cell Transplantation From Related Donors in Treating Patients With Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndrome, or Aplastic Anemia - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002718

Purpose

RATIONALE: Bone marrow and peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of T-cell depleted bone marrow and G-CSF stimulated peripheral stem cell transplantation in treating patients with leukemia, lymphoblastic lymphoma, myelodysplastic syndrome, or aplastic anemia.

Condition	Intervention	Phase
Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Biological: filgrastim Drug: cyclophosphamide Drug: cytarabine Drug: methylprednisolone Drug: thiotepa Procedure: in vitro-treated bone marrow transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A PHASE II TRIAL OF T-CELL DEPLETED MARROW GRAFTS COMBINED WITH INFUSIONS OF G-CSF STIMULATED, CD34 CEPRATE STEM CELL COLUMN SELECTED, E-ROSETTE DEPLETED PERIPHERAL BLOOD PROGENITOR CELLS DERIVED FROM HLA HAPLOTYPE MATCHED RELATED DONORS FOR PATIENTS WITH LEUKEMIA LACKING AN HLA-MATCHED RELATED OR UNRELATED DONOR

Resource links provided by NLM:

MedlinePlus related topics: Anemia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Cyclophosphamide Thiotepa Cytarabine hydrochloride Methylprednisolone Filgrastim Cytarabine

U.S. FDA Resources

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

Study Start Date:

November 1995

Detailed Description:

OBJECTIVES:

Determine the potential of T-cell-depleted bone marrow and peripheral blood stem cells (PBSC) from HLA-haplotype, partially matched related donors to induce extended disease-free survival in patients with leukemia, lymphoblastic lymphoma, myelodysplastic syndrome, or severe aplastic anemia who would otherwise be ineligible for transplantation because of the lack of an HLA-identical related or unrelated donor.
Determine the impact of filgrastim (G-CSF)-stimulated, CD34+, E-rosette and T-cell-depleted PBSC derived from an HLA-haplotype, partially matched donor on the incidence and quality of engraftment, kinetics, and quality of hematopoietic and immunologic reconstitution, and incidence and severity of graft-versus-host disease (GVHD) in these patients.
Correlate the doses of PBSC and clonable T-cells with the incidence of engraftment, extent of chimerism, incidence and severity of acute and chronic GVHD, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival rates at 2-4 years after transplantation in these patients.

OUTLINE: Patients are stratified by number of HLA-incompatible alleles (1 vs 2 or 3).

Harvest: Beginning 6-10 days before transplantation, allogeneic bone marrow is harvested and treated in vitro. Beginning 5-6 days before transplantation, filgrastim (G-CSF)-stimulated, allogeneic peripheral blood stem cells (PBSC) are harvested, selected for CD34+ cells, and treated in vitro. If feasible, autologous bone marrow is harvested in the event of allogeneic graft failure.
Myeloablation: Patients undergo total body irradiation 3 times a day on days -9 to -6, thiotepa IV over 4 hours on days -5 and -4, and cyclophosphamide IV on days -3 and -2.
Transplantation: CD34+, E-rosette and T-cell-depleted PBSC are infused over 15 minutes and then T-cell-depleted bone marrow is infused over 1-5 minutes on day 0. Patients receive G-CSF IV over 30 minutes beginning on day 1 and continuing until blood counts recover and then tapering. Patients receive anti-thymocyte globulin IV over 4-6 hours on days 8, 10, 12, and 14 and oral methylprednisolone on days 8-14 followed by tapered doses on days 15-17.
CNS prophylaxis: Beginning at least 2 months after transplantation, patients with acute lymphocytic leukemia (ALL) and no history of CNS leukemia receive cytarabine intrathecally (IT) monthly for 6 months and patients with ALL and a history of CNS leukemia receive cytarabine IT monthly for 12 months.

Patients with graft failure are offered autologous bone marrow transplantation (BMT) or second allogeneic BMT.

Patients are followed at 1, 3, 6, and 12 months and then annually for 3 years.

PROJECTED ACCRUAL: A total of 60 patients (30 patients per stratum) will be accrued for this study at a rate of 15 leukemia patients and 5 aplastic anemia patients per year.

Eligibility

Ages Eligible for Study:	up to 49 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

One of the following diagnoses:
- Acute myelogenous leukemia (AML) meeting 1 of the following conditions:
  - Failed to achieve first remission after an intensive induction regimen containing an anthracycline and cytarabine
  - In second remission and not enrolled in a protocol for autologous bone marrow transplantation
  - Failed to achieve or sustain second remission
  - In first remission but at high risk of relapse because of 1 of the following factors:
    - High-risk cytogenetic features (monosomy 7,5q-, trisomy 8, or t(9;22))
    - AML secondary to treatment of a prior malignancy and without good-risk cytogenetic features of t(8;21), t(15;17), or inv 16
    - AML secondary to myelodysplastic disease
- Acute lymphocytic leukemia (ALL) meeting 1 of the following conditions:
  - In second remission with initial relapse occurring within 2 years of diagnosis
  - In first complete remission with high-risk cytogenetics (t(9;22) or t(4;11))
  - In third or subsequent remission
  - Failed to achieve or sustain a second remission
- Chronic myelogenous leukemia (CML) in first or second chronic phase or accelerated phase
- Stage IV lymphoblastic lymphoma not in first remission or that failed to achieve a remission within the first 4 weeks of induction therapy
- Juvenile CML
- Myelodysplastic syndrome
- Severe aplastic anemia unresponsive to anti-thymocyte globulin or cyclosporine
No CNS or skin involvement with leukemia
No requirement for mediastinal irradiation
No healthy, HLA-identical related donor of at least 1 year of age or matched unrelated donor available within 4-6 months
Availability of a healthy, 1-3 HLA-A, -B, and -DR mismatched related donor
- Willing and able to undergo general anesthesia for marrow donation and a 5-day course of filgrastim (G-CSF) with 2 daily leukaphereses

PATIENT CHARACTERISTICS:

Age:

Under 50 (50 and over allowed on a case-by-case basis)

Performance status:

Age 16 and over:
- Karnofsky 70-100%
Under age 16:
- Lansky 50-100%

Hematopoietic:

Not specified

Hepatic:

Bilirubin less than 2.0 mg/dL (in the absence of liver involvement)
AST less than twice normal (in the absence of liver involvement)

Renal:

Creatinine normal OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

Asymptomatic or LVEF greater than 50% at rest, with improvement during exercise

Pulmonary:

Asymptomatic or DLCO greater than 50% predicted (corrected for hemoglobin)

Other:

No known hypersensitivity to mouse protein or chicken egg products
No active viral, bacterial, or fungal infection
HIV-1, HIV-2, HTLV-1, and HTLV-2 negative
No other concurrent medical condition that would preclude transplantation
Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002718

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Richard J. O'Reilly, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000064557, MSKCC-95084, NCI-V96-0809
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00002718 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission

stage IV adult lymphoblastic lymphoma
recurrent adult lymphoblastic lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
juvenile myelomonocytic leukemia
childhood chronic myelogenous leukemia
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
chronic myelomonocytic leukemia
childhood myelodysplastic syndromes

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Preleukemia
Pathologic Processes
Therapeutic Uses
Methylprednisolone Hemisuccinate
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Glucocorticoids
Thiotepa
Neoplasms
Antimetabolites
Leukemia, Lymphoid
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Prednisolone acetate
Cyclophosphamide
Neuroprotective Agents

ClinicalTrials.gov processed this record on November 30, 2009