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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

Primary Purpose

Leukemia, Lymphoma, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
filgrastim
cyclophosphamide
cytarabine
methylprednisolone
thiotepa
in vitro-treated bone marrow transplantation
in vitro-treated peripheral blood stem cell transplantation
radiation therapy
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, chronic myelomonocytic leukemia, childhood myelodysplastic syndromes

Eligibility Criteria

undefined - 49 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Candidates for transplant

Arm Description

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.

Outcomes

Primary Outcome Measures

overall disease survival

Secondary Outcome Measures

To correlate progenitor cell doses and doses of clonable T-cells

Full Information

First Posted
November 1, 1999
Last Updated
December 21, 2015
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002718
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
November 1995 (undefined)
Primary Completion Date
January 2004 (Actual)
Study Completion Date
October 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
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, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, chronic myelomonocytic leukemia, childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Candidates for transplant
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated peripheral blood stem cell transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
overall disease survival
Time Frame
2 to 4 years post transplant
Secondary Outcome Measure Information:
Title
To correlate progenitor cell doses and doses of clonable T-cells
Time Frame
2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard J. O'Reilly, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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