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

NCT00002718 | Completed Phase 2

• 4 other identifiers: 95-084P30CA008748MSKCC-95084NCI-V96-0809
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• overall disease survival

  2 to 4 years post transplant

Secondary Outcomes (1)

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

  2 years

Study Arms (1)

Candidates for transplant

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.

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

Interventions

anti-thymocyte globulin BIOLOGICAL

Candidates for transplant

filgrastim BIOLOGICAL

Candidates for transplant

cyclophosphamide DRUG

Candidates for transplant

cytarabine DRUG

Candidates for transplant

methylprednisolone DRUG

Candidates for transplant

thiotepa DRUG

Candidates for transplant

in vitro-treated bone marrow transplantation PROCEDURE

Candidates for transplant

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

Candidates for transplant

radiation therapy RADIATION

Candidates for transplant

Eligibility Criteria

• Age: Up to 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders; Leukemia, Myelomonocytic, Chronic

Interventions

Antilymphocyte Serum; Filgrastim; Cyclophosphamide; Cytarabine; Methylprednisolone; Thiotepa; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Triethylenephosphoramide; Aziridines; Azirines; Therapeutics

Study Officials

• Richard J. O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: November 1, 1995
• Primary Completion: January 1, 2004
• Study Completion: October 1, 2008
• Last Updated: December 23, 2015

Record last verified: 2015-12

Locations

US (1)