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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00080925
First received: April 7, 2004
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Biological: filgrastim
Biological: graft-versus-tumor induction therapy
Biological: rituximab
Biological: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: cytarabine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: fludarabine phosphate
Drug: prednisone
Drug: vincristine sulfate
Procedure: peripheral blood stem cell transplantation
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: T-Cell Depleted, Reduced-Intensity Allogeneic Stem Cell Transplantation From Haploidentical Related Donors For Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 20
Study Start Date: February 2004
Study Completion Date: December 2010
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00080925

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: Michael R. Bishop, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00080925     History of Changes
Other Study ID Numbers: 040116, 04-C-0116, CDR0000357432
Study First Received: April 7, 2004
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
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

Additional relevant MeSH terms:
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases
Cyclophosphamide
Doxorubicin
Fludarabine

ClinicalTrials.gov processed this record on November 23, 2014