Completed

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

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What is being tested

anti-thymocyte globulin

+ filgrastim

+ cyclophosphamide

BiologicalDrugProcedureRadiation
Who is being recruted

Bone Marrow Diseases+25

+ Chronic Disease

+ Hematologic Diseases

Until 49 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: November 1995
See protocol details

Summary

Principal SponsorMemorial Sloan Kettering Cancer Center
Last updated: December 23, 2015
Sourced from a government-validated database.Claim as a partner

Study start date: November 1, 1995

Actual date on which the first participant was enrolled.

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.

NCT00002718
Principal SponsorMemorial Sloan Kettering Cancer Center
Last updated: December 23, 2015
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

31 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Until 49 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Bone Marrow DiseasesChronic DiseaseHematologic DiseasesHemic and Lymphatic DiseasesImmune System DiseasesImmunoproliferative DisordersLeukemia, LymphoidLeukemia, MyeloidLymphatic DiseasesLymphoproliferative DisordersNeoplasmsNeoplasms by Histologic TypePathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveDisease AttributesLeukemiaLymphomaMyelodysplastic SyndromesMyeloproliferative DisordersLeukemia, Myeloid, Accelerated PhaseLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, AcuteLeukemia, Myelomonocytic, ChronicPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myelomonocytic, JuvenileMyelodysplastic-Myeloproliferative DiseasesLeukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

One single intervention group is designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
Pts stratified by number of HLA-incompatible alleles(1 vs 2 or 3). Harvest:Begin 6-10 d before transplant,allogeneic BM is harvest & tx in vitro. Begin 5-6 d before transplant,G-CSF-stimulated,PBSC harvest,selected for CD34+ cells,& treatment in vitro. If doable,ABM harvest in event of allogeneic graft failure. Myeloablation:Pts u/g TBI 3x d days -9 to -6, thiotepa IV over 4hrs days -5 & -4, & cyclophosphamide IV days -3 & -2. Transplant:CD34+, E-rosette & T-cell-depleted PBSC infuse over 15mins & T-cell-depleted bone marrow infused over 1-5mins day 0. Pts get G-CSF IV over 30 min begin day 1 & continue til blood counts recover & tapering. Pts get anti-thymocyte globulin IV over 4-6hrs days 8,10,12,&14 & oral methylprednisolone days 8-14 followed by tapered doses days 15-17. See detailed description for more details.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 1 location

Memorial Sloan-Kettering Cancer Center

New York, United StatesOpen Memorial Sloan-Kettering Cancer Center in Google Maps
CompletedOne Study Center