Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

NCT00544115 | Active Not Recruiting Phase 2 Results

• 4 other identifiers: 01089P30CA033572CHNMC-01089CDR0000566376
• Study Type: interventional
• Target: 260
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, and sirolimus before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well donor peripheral stem cell transplant works in treating patients with advanced hematologic cancer or other disorders.

Conditions

Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition

Keywords

graft versus host disease; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; atypical chronic myeloid leukemia; chronic myelomonocytic leukemia; juvenile myelomonocytic leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia; adult acute myeloid leukemia in remission; childhood acute myeloid leukemia in remission; secondary acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic eosinophilic leukemia; chronic idiopathic myelofibrosis; chronic neutrophilic leukemia; essential thrombocythemia; polycythemia vera; Waldenstrom macroglobulinemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent adult Burkitt lymphoma; 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 mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; splenic marginal zone lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; childhood nasal type extranodal NK/T-cell lymphoma; recurrent childhood large cell lymphoma; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; recurrent childhood lymphoblastic lymphoma; Burkitt lymphoma; recurrent childhood small noncleaved cell lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; recurrent adult T-cell leukemia/lymphoma; recurrent adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; refractory chronic lymphocytic leukemia; refractory multiple myeloma; stage III multiple myeloma; aplastic anemia; paroxysmal nocturnal hemoglobinuria; adult acute lymphoblastic leukemia in remission; childhood acute lymphoblastic leukemia in remission; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; stage II multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Neutrophil Engraftment - The Days Till ANC Recovery

  The primary engraftment endpoint, neutrophil engraftment, is defined as the first of three consecutive days on which the absolute neutrophil count is \> 500/µL. The duration and extent of neutrophil engraftment is the time from transplant to neutrophil engraftment.

  Up to 180 days post transplant

Secondary Outcomes (1)

• Two-year Overall Survival

  Up to 2 years post transplant

Study Arms (6)

Regimen I

ACTIVE COMPARATOR

Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.

Drug: cyclophosphamide; Drug: cyclosporine; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

Regimen II

ACTIVE COMPARATOR

Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.

Drug: busulfan; Drug: cyclophosphamide; Drug: cyclosporine; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Regimen III

ACTIVE COMPARATOR

Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.

Drug: cyclosporine; Drug: etoposide; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

Regimen IV

ACTIVE COMPARATOR

Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.

Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Regimen V

ACTIVE COMPARATOR

Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.

Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

Regimen VI

ACTIVE COMPARATOR

Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.

Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: sirolimus; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

tacrolimus DRUG

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

busulfan DRUG

Regimen II; Regimen VI

cyclophosphamide DRUG

Regimen I; Regimen II

cyclosporine DRUG

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

etoposide DRUG

Regimen III

fludarabine phosphate DRUG

Regimen IV; Regimen V; Regimen VI

melphalan DRUG

Regimen IV

methotrexate DRUG

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

mycophenolate mofetil DRUG

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

sirolimus DRUG

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

allogeneic hematopoietic stem cell transplantation PROCEDURE

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

peripheral blood stem cell transplantation PROCEDURE

Regimen I; Regimen II; Regimen III; Regimen IV; Regimen V; Regimen VI

total-body irradiation RADIATION

Regimen I; Regimen III; Regimen V

Eligibility Criteria

• Age: 0 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of one of the following: * Acute lymphocytic leukemia (ALL), meeting one of the following criteria: * In first relapse or beyond * High-risk ALL, defined by any of the following: * Hypoploidy (≤ 44 chromosomes) * Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL * Elevated WBC at presentation (WBC \> 20,000/mm³ \[for patients \> 18 years of age\]; WBC \> 200,000/mm³ \[for patients 12-18 years of age\]) * Acute myeloid leukemia (AML), meeting one of the following criteria: * In first complete remission * Failed to achieve remission * In first relapse or beyond * Secondary AML (\> 30% blasts in marrow aspirate) * Should receive induction chemotherapy to obtain remission, if possible, before transplant * Chronic myelogenous leukemia, meeting one of the following criteria: * In first or second chronic phase or accelerated phase * In blast crisis, defined as \> 30% promyelocytes plus blasts in the bone marrow * Myelodysplastic syndromes, including any of the following: * Refractory anemia with excess blasts (RAEB) * Chronic myelomonocytic leukemia * RAEB in transformation * Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma * Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy * Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis * Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation * Patients \> 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible * No uncontrolled CNS involvement of disease * No matched (6/6) related donor available * HLA-identical unrelated donor available * HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens * Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors * Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant PATIENT CHARACTERISTICS: * Karnofsky performance status 50-100% * Life expectancy \> 8 weeks * LVEF ≥ 45% at rest * AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease) * Total bilirubin \< 1.5 times normal (unless liver function abnormality is due to underlying disease) * Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min * DLCO ≥ 40% of predicted (corrected for hemoglobin) * No coexisting medical problem that would significantly increase the risk of the transplant procedure * HIV negative * Not pregnant PRIOR CONCURRENT THERAPY: * See Disease Characteristics

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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Myeloproliferative Disorders; Graft vs Host Disease; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Precancerous Conditions; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Pdgfra-Associated Chronic Eosinophilic Leukemia; Primary Myelofibrosis; Leukemia, Neutrophilic, Chronic; Thrombocythemia, Essential; Polycythemia Vera; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Extranodal NK-T-Cell; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Hodgkin Disease; Recurrence; Anemia, Aplastic; Hemoglobinuria, Paroxysmal; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Interventions

Busulfan; Cyclophosphamide; Cyclosporine; Etoposide; fludarabine phosphate; Melphalan; Methotrexate; Mycophenolic Acid; Sirolimus; Tacrolimus; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. Monzr Al Malki, MD
• Organization: City of Hope

malmalki@coh.org

626359811

Study Officials

• Auayporn P. Nademanee, MD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2007
• First Posted: October 16, 2007
• Study Start: October 16, 2001
• Primary Completion: March 13, 2007
• Study Completion: April 2, 2026
• Last Updated: June 10, 2025
• Results First Posted: May 10, 2023

Record last verified: 2025-05