Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

NCT00296023 | Completed DMC

• 4 other identifiers: CDR0000463724UCSF-98251UCSF-9805UCSF-H9996-15837-06
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.

Conditions

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

Keywords

stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; noncontiguous stage II marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; noncontiguous stage II mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; stage II multiple myeloma; stage III multiple myeloma; chronic phase chronic myelogenous leukemia; primary myelofibrosis; polycythemia vera; prolymphocytic leukemia; stage II adult Hodgkin lymphoma; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; chronic myelomonocytic leukemia; adult acute myeloid leukemia in remission; secondary acute myeloid leukemia; Waldenström macroglobulinemia; essential thrombocythemia; 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); noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; stage I multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Toxicity and survival

  up to 36 months post transplant

Study Arms (1)

stem cell transplant

EXPERIMENTAL

Biological: anti-thymocyte globulin; Biological: filgrastim; Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Interventions

anti-thymocyte globulin BIOLOGICAL

stem cell transplant

filgrastim BIOLOGICAL

stem cell transplant

therapeutic allogeneic lymphocytes BIOLOGICAL

stem cell transplant

busulfan DRUG

stem cell transplant

fludarabine phosphate DRUG

stem cell transplant

methotrexate DRUG

stem cell transplant

tacrolimus DRUG

stem cell transplant

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

stem cell transplant

peripheral blood stem cell transplantation PROCEDURE

stem cell transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of a high-risk indolent hematologic malignancy meeting the following criteria: * Chronic lymphocytic leukemia (CLL) meeting 1 of the following criteria: * In second or subsequent remission * Failed to achieve a complete remission (CR) after chemotherapy * Non-Hodgkin's lymphoma (NHL) meeting 1 of the following criteria: * Low-grade NHL meeting 1 of the following criteria: * Standard-risk disease in second or subsequent remission * Standard-risk disease and failed to achieve a CR after chemotherapy * In first or subsequent remission with adverse International Prognostic Index (IPI) prognostic features, as defined by the presence of ≥ 3 of the following: * Age \> 60 years * Tumor stage III or IV * Extranodal disease at \> 1 site * ECOG performance status ≥ 2 * Serum lactic dehydrogenase (LDH) \> upper limit of normal (ULN) * Intermediate- or high-grade NHL meeting 1 of the following criteria: * In second or subsequent remission * Failed to achieve a CR after initial chemotherapy * Waldenstrom's macroglobulinemia meeting 1 of the following criteria: * In second or subsequent remission * Failed to achieve a CR after initial chemotherapy * Multiple myeloma meeting 1 of the following criteria: * In first or subsequent remission * Failed to achieve a CR after initial chemotherapy * Myeloproliferative disorders, including any of the following: * Chronic myelogenous leukemia in first or subsequent chronic phase * Myelofibrosis * Essential thrombocytopenia that is poorly responsive to standard therapy * Polycythemia vera that is poorly responsive to standard therapy or is in spent phase * Prolymphocytic leukemia meeting 1 of the following criteria: * In first or subsequent remission * Failed to achieve a CR after initial chemotherapy * Mantle cell lymphoma meeting 1 of the following criteria: * In first or subsequent remission * Failed to achieve a CR after initial chemotherapy * Hodgkin's lymphoma meeting the following criteria: * In second or subsequent remission * Prior remission duration \> 6 months * No radiation therapy as the only prior primary therapy * Myelodysplastic syndromes (MDS) meeting 1 of the following criteria: * Refractory anemia with excess blasts (RAEB) * RAEB in transformation * Chronic myelomonocytic leukemia * Any MDS with transfusion dependence * Any MDS with ≥ 2 significant infections * Acute myeloid leukemia in morphologic remission * In CR or partial remission or stabilization of disease after standard chemotherapy * No progressive or refractory disease * Not eligible for standard allogeneic bone marrow transplantation * Meets 1 of the following criteria: * Age 60 to 75 years old AND no co-morbid illness * Younger patients with any of the following comorbidities: * Decreased cardiac ejection fraction * Pulmonary dysfunction * Elevated liver function tests * Hepatitis C infection * Poor performance status * Sibling or related donor available * Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: * See Disease Characteristics * ECOG performance status 0-2 * Creatinine \< 2.0 mg/dL * Creatinine clearance \> 40 mL/min * Ejection fraction \> 30% by echocardiogram or MUGA * Bilirubin \< 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal) * Alkaline phosphatase \< 4 times ULN * AST \< 4 times ULN * HIV negative * Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation * No active infection 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

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Alta Bates Comprehensive Cancer Center

Berkeley, California, 94704, United States

Location

UCSF Comprehensive Cancer Center

San Francisco, California, 94143-0324, United States

Location

MeSH Terms

Conditions

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

Interventions

Antilymphocyte Serum; Filgrastim; Busulfan; fludarabine phosphate; Methotrexate; Tacrolimus; 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, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Anemia, Refractory; Anemia; Myelodysplastic-Myeloproliferative Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Thomas G. Martin, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Willis Navarro, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Charles A. Linker, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2006
• First Posted: February 24, 2006
• Study Start: January 1, 1999
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2008
• Last Updated: October 4, 2012

Record last verified: 2012-10

Locations

US (2)