Alemtuzumab Plus Fludarabine and Melphalan With or Without Cyclosporine, Mycophenolate Mofetil, and Low-Dose Total-Body Irradiation Therapy Followed by Donor Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer

NCT00085449 | Withdrawn Phase 1

• 2 other identifiers: CALGB-100102CDR0000370797
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 24

Brief Summary

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects of alemtuzumab, fludarabine, and melphalan with or without cyclosporine, mycophenolate mofetil, and total-body irradiation before donor peripheral blood stem cell transplant and to see how well they work in treating patients with relapsed or refractory hematologic cancer.

Conditions

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

Keywords

recurrent adult acute myeloid leukemia; adult acute myeloid leukemia in remission; recurrent adult acute lymphoblastic leukemia; adult acute lymphoblastic leukemia in remission; myelodysplastic/myeloproliferative neoplasm, unclassifiable; previously treated myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative; chronic myelomonocytic leukemia; recurrent adult Burkitt lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent small lymphocytic lymphoma; recurrent marginal zone lymphoma; recurrent mantle cell lymphoma; recurrent adult lymphoblastic lymphoma; accelerated phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; refractory chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; refractory multiple myeloma; secondary myelodysplastic syndromes; de novo myelodysplastic syndromes; 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)

Outcome Measures

Primary Outcomes (3)

• Engraftment rate

  Up to 6 years

• Risk of graft-vs-host disease

  Up to 6 years

• Progression-free survival (PFS)

  Up to 6 years

Study Arms (1)

Regimen A + B

EXPERIMENTAL

Conditioning regimen A: Patients receive alemtuzumab IV over 2 hours on days -14 to -12; fludarabine IV over 30 minutes on days -7 to -3; and melphalan IV over 20-30 minutes on day -2. Conditioning regimen B: Patients receive oral or IV cyclosporine twice daily and oral or IV mycophenolate mofetil twice daily on days -15 to 0. Patients also receive alemtuzumab, fludarabine, and melphalan as in conditioning regimen A. Patients undergo low-dose total body irradiation twice daily on days -2 and -1. All patients undergo allogeneic, T-cell-depleted, CD34-positive peripheral blood stem cell transplantation on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 1 and continuing until blood counts recover. Patients are followed every 3 months for 1 year and then every 6 months for 5 years.

Biological: alemtuzumab; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: melphalan; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

alemtuzumab BIOLOGICAL

Regimen A + B

cyclosporine DRUG

Regimen A + B

fludarabine phosphate DRUG

Regimen A + B

melphalan DRUG

Regimen A + B

mycophenolate mofetil DRUG

Regimen A + B

peripheral blood stem cell transplantation PROCEDURE

Regimen A + B

radiation therapy RADIATION

Regimen A + B

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed hematological malignancy of 1 of the following types: * Acute myeloid leukemia meeting at least 1 of the following criteria: * Poor-risk cytogenetics, including -5, 5q-, -7, 7q-, 11q23, and Philadelphia (Ph) chromosome-positive in first or subsequent complete remission (CR) * Relapsed or primary refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow * Standard-risk cytogenetics in second CR AND autologous transplantation is not feasible * Standard-risk cytogenetics in third or subsequent CR * Acute lymphoblastic leukemia meeting 1 of the following criteria: * Second or subsequent CR * High-risk cytogenetics, including Ph chromosome-positive and t(4:11) in first CR * Relapsed or primarily refractory disease with ≤ 10% blasts in the peripheral blood and ≤ 20% blasts in the bone marrow * High-risk myelodysplasia * International Prognostic Scoring System Score ≥ 2.5 * Chronic myeloid leukemia (CML)\* with an inadequate response to imatinib meeting 1 of the following criteria: * Second or subsequent chronic phase * Accelerated phase NOTE: \*Patients with CML in blast crisis (\> 30% promyelocytes and myeloblasts in the bone marrow) are not eligible * Non-Hodgkin's lymphoma meeting 1 of the following criteria: * Primarily refractory disease or in refractory relapse * Relapsed disease after autologous stem cell transplantation * Chemosensitive relapsed disease without CR to standard salvage therapy AND no option for autologous stem cell transplantation due to blood or marrow involvement or failure to harvest sufficient autologous stem cells * Chronic lymphocytic leukemia meeting both of the following criteria: * Stage III or IV disease * Refractory to fludarabine * Multiple myeloma meeting 1 of the following criteria: * Primarily refractory disease or in refractory relapse * Relapsed disease after autologous stem cell transplantation * No relapsed disease \< 6 months after autologous stem cell transplantation * No available eligible HLA-matched (i.e., 5 of 6 or 6 of 6 antigen match for HLA-A, -B, and -DR loci) family donor by serological or molecular typing * Available suitable family donor meeting the following criteria: * Parent, sibling, or child of the recipient * ≥ 16 years of age * Identical for only one HLA haplotype (i.e., haploidentical) AND incompatible at the HLA-A, -B, -C, and -DR loci of the unshared haplotype by serological or molecular typing * Mismatched with respect to KIR class I epitopes graft-vs-host directional activity * Mismatching that predicts both graft-vs-host and host-vs-graft bi-directional activity eligible * No mismatching that predicts only host-vs-graft directional activity PATIENT CHARACTERISTICS: Age * 18 to 60 Performance status * ECOG 0-1 Hepatic * Bilirubin \< 2 times upper limit of normal (ULN) * AST and ALT \< 2 times ULN Renal * Creatinine ≤ 2 mg/dL Cardiovascular * LVEF \> 40% (corrected) Pulmonary * DLCO \> 50% of predicted Other * No active infection requiring oral or IV antibiotics * HIV negative * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics Chemotherapy * See Disease Characteristics Endocrine therapy * Concurrent corticosteroids allowed for adrenal failure, treatment of graft-vs-host disease, or as premedication during study * No concurrent corticosteroids for antiemesis

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

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (24)

Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, 52242-1009, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, 07503, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1082, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University

Columbus, Ohio, 43210-1240, United States

Location

Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myeloproliferative Disorders; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Burkitt Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Lymphoma, Large B-Cell, Diffuse; Congenital Abnormalities

Interventions

Alemtuzumab; Cyclosporine; fludarabine phosphate; Melphalan; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Sherif S. Farag, MD, PhD

  Indiana University Melvin and Bren Simon Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2004
• First Posted: June 11, 2004
• Study Start: May 1, 2006
• Primary Completion: January 1, 2007
• Study Completion: January 1, 2007
• Last Updated: November 27, 2019

Record last verified: 2019-11

Locations

US (24)