T-Cell-Depleted Allogeneic Stem Cell Transplantation After Immunoablative Induction Chemotherapy and Reduced-Intensity Transplantation Conditioning in Treating Patients With Hematologic Malignancies

NCT00080925 | Completed Phase 1

• 3 other identifiers: 04011604-C-0116CDR0000357432
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Donor peripheral stem cell transplantation may be able to replace bone marrow and immune cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor are rejected by the body's normal cells. Eliminating the T cells from the donor cells before transplanting them and giving cyclosporine may prevent this from happening. PURPOSE: This phase I trial is studying the side effects of T-cell-depleted allogeneic stem cell transplantation after immunoablative induction chemotherapy and reduced-intensity transplantation conditioning (chemotherapy) in treating patients with hematologic malignancies.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms

Keywords

prolymphocytic leukemia; accelerated phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; recurrent adult Hodgkin lymphoma; refractory anemia with excess blasts; refractory multiple myeloma; primary myelofibrosis; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult Burkitt lymphoma; recurrent mantle cell lymphoma; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; chronic myelomonocytic leukemia; polycythemia vera; essential thrombocythemia; stage II multiple myeloma; stage III multiple myeloma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12)

Interventions

filgrastim BIOLOGICAL

graft-versus-tumor induction therapy BIOLOGICAL

rituximab BIOLOGICAL

therapeutic allogeneic lymphocytes BIOLOGICAL

cyclophosphamide DRUG

cyclosporine DRUG

cytarabine DRUG

doxorubicin hydrochloride DRUG

etoposide DRUG

fludarabine phosphate DRUG

prednisone DRUG

vincristine sulfate DRUG

peripheral blood stem cell transplantation PROCEDURE

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following hematologic malignancies: * Acute myeloid leukemia (AML), meeting 1 of the following criteria: * In first complete remission (CR1), meeting 1 of the following criteria: * Adverse cytogenetics with minimal residual disease detectable by flow cytometry, cytogenetic analysis, fluorescence in situ hybridization (FISH), or polymerase chain reaction (PCR), defined as 1 of the following: * Complex karyotype \[≥ 3 abnormalities\] * inv(3) or t(3;3) * t(6;9) * t(6;11) * Monosomy 7 * Trisomy 8, alone or with an abnormality other than t(8;21), t(9;11), inv(16), or t(16;16) * t(11;19) (q23;p13.1) * Failed to achieve CR after primary induction chemotherapy * Secondary AML * In second or subsequent remission (CR2 or greater) * Acute lymphoblastic leukemia, meeting 1 of the following criteria: * In CR1, meeting 1 of the following criteria: * Adverse cytogenetics with minimal residual disease detectable by flow cytometry, cytogenetic analysis, FISH, or PCR, defined as the following: * Translocations involving 11q23, t(9;22), or bcr-abl rearrangement * Failed to achieve CR after primary induction chemotherapy * In CR2, if CR1 was \< 12 months * In CR3 or greater * Myelodysplastic syndromes (MDS) * INT-2 or high-risk by International Prognostic Scoring System * No MDS with Fanconi anemia * Chronic myelogenous leukemia (CML), meeting 1 of the following criteria: * Accelerated phase with treatment failure after imatinib mesylate * Blast phase * Myeloproliferative disorders, meeting 1 of the following criteria: * Agnogenic myeloid metaplasia with adverse-risk features, meeting at least 2 of the following criteria: * Hemoglobin \< 10 g/dL or \> 10g/dL if transfusion-dependent * WBC \< 4,000/mm\^3 OR \> 30,000/mm\^3 OR requires cytoreductive therapy to maintain WBC \< 30,000/mm\^3 * Abnormal cytogenetics, including +8, 12p- * Polycythemia vera or essential thrombocythemia in transformation to secondary AML * Myelodysplastic/myeloproliferative disease * Chronic myelomonocytic leukemia * Hodgkin's lymphoma or non-Hodgkin's lymphoma * Refractory lymphoma with progressive disease during combination chemotherapy * Relapse after OR ineligible for autologous stem cell transplantation (SCT) * Chronic lymphocytic leukemia * Treatment failure\* after fludarabine, chlorambucil, and at least 1 other salvage regimen * Prolymphocytic leukemia (PLL), meeting 1 of the following criteria: * T-PLL * Treatment failure\* after alemtuzumab and at least 1 other regimen * B-PLL * Treatment failure\* after fludarabine and at least 1 other salvage regimen * Multiple myeloma, meeting 1 of the following criteria: * Relapse after autologous SCT * Plasma cell leukemia * Adverse cytogenetics, defined as 1 of the following: * del(13q) = 11q translocation NOTE: \*Treatment failure is defined as relapse within 6 months OR failure to achieve remission * Less than 10% blasts in bone marrow and no circulating blasts in peripheral blood for the following diagnoses: * Primary or secondary leukemia * Refractory anemia with excess blasts * CML * Other eligible diagnosis in transformation to acute leukemia * Expected survival of approximately 1 year or less with conventional therapy * No active CNS involvement by malignancy\* * Prior CNS involvement with no current evidence of CNS malignancy allowed NOTE: \*Active CNS malignancy is defined by lymphoma: tumor mass on CT scan or leptomeningeal disease OR leukemia: blasts present on cerebrospinal fluid cytospin * Availability of a donor who is a sibling, parent, or offspring who shares 1 full haplotype (HLA-A, -B, or -DR) * Recipient and donor must have at least a 2-antigen disparity in either the host-versus-graft or graft-versus-host direction * Parent or offspring donor who is mismatched for a single HLA antigen (i.e., 5/6 HLA) is allowed * No sibling donor who is 6/6 HLA-matched OR mismatched for a single HLA antigen (i.e., 5/6 HLA) * No unrelated donor identified in a prior or current National Marrow Donor Program registry search PATIENT CHARACTERISTICS: Age * 18 to 55 Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * At least 3 months Hematopoietic * See Disease Characteristics * Absolute neutrophil count ≥ 1,000/mm\^3\* * Platelet count ≥ 20,0000/mm\^3\* (without transfusion) NOTE: \*Lower values may be accepted at the discretion of the principal investigator or study chairperson if due to bone marrow involvement by malignancy Hepatic * ALT and AST ≤ 2.5 times upper limit of normal (ULN)\* * Bilirubin ≤ 2.5 times ULN\* * Unconjugated hyperbilirubinemia consistent with Gilbert's syndrome allowed * No chronic active hepatitis B infection * Hepatitis B core antibody positive allowed provided patient is surface antigen negative and has no evidence of active infection * No hepatitis C viral infection * Seronegative for anti-hepatitis C antibody and detectable hepatitis C viral RNA by reverse transcriptase-polymerase chain reaction assay NOTE: \*Higher levels may be accepted at the discretion of the principle investigator or study chairperson if such elevations are due to liver involvement by malignancy Renal * Creatinine ≤ 1.5 mg/dL OR * Creatinine clearance ≥ 50 mL/min Cardiovascular * LVEF ≥ 45% Pulmonary * DLCO ≥ 50% of expected value (corrected for blood hemoglobin level and alveolar volume) Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 1 year after study participation * HIV negative * No active infection not responding to antimicrobial therapy * No psychiatric disorder that would preclude study compliance or informed consent PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * At least 2 weeks since prior monoclonal antibody therapy Chemotherapy * See Disease Characteristics * At least 2 weeks since prior systemic chemotherapy Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * Recovered from all prior therapy * No administration of tyrosine kinase (TK) inhibitors, including imatinib mesylate and dasatinib, during the conditioning regimen; TK inhibitor administration may resume 28 days after transplantation

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

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Prolymphocytic; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Anemia, Refractory, with Excess of Blasts; Primary Myelofibrosis; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Burkitt Lymphoma; Lymphoma, Mantle-Cell; Leukemia, Myelomonocytic, Chronic; Polycythemia Vera; Thrombocythemia, Essential; Lymphoma, B-Cell, Marginal Zone; Congenital Abnormalities

Interventions

Filgrastim; Rituximab; Cyclophosphamide; Cyclosporine; Cytarabine; Doxorubicin; Etoposide; fludarabine phosphate; Prednisone; Vincristine; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Anemia, Refractory; Anemia; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Michael R. Bishop, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 7, 2004
• First Posted: April 8, 2004
• Study Start: February 1, 2004
• Study Completion: December 1, 2010
• Last Updated: March 8, 2012

Record last verified: 2012-03

Locations

US (1)