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Sirolimus in Preventing Graft-Versus-Host Disease in Patients With Hematologic Malignancies Who Are Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), November 2007
First Received: February 10, 2004   Last Updated: October 10, 2009   History of Changes
Sponsor: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00077480
  Purpose

RATIONALE: Sirolimus may be effective in preventing graft-versus-host disease in patients who are undergoing allogeneic stem cell transplantation.

PURPOSE: This phase II trial is studying four different regimens of sirolimus-treated T cells and/or sirolimus by mouth and comparing how well they work in preventing graft-versus-host disease in patients who are undergoing allogeneic hematopoietic stem cell transplantation for hematologic malignancies .


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: therapeutic allogeneic lymphocytes
Drug: sirolimus
Phase II

Study Type: Interventional
Study Design: Supportive Care, Active Control
Official Title: Pilot Study Of Sirolimus (Rapamycin) Generated Donor Th2 Cells And In Vivo Sirolimus For GVHD Prevention After Allogeneic HSCT For Hematologic Malignancy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety and feasibility [ Designated as safety issue: Yes ]
  • Graft-versus-host disease rate [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pattern of post-transplantation CD4+ and CD8+ T-cell production of Th1- and Th2-type cytokines [ Designated as safety issue: No ]
  • Kinetics of alloengraftment [ Designated as safety issue: No ]
  • Incidence of opportunistic infection [ Designated as safety issue: Yes ]
  • Incidence of malignant disease in complete remission [ Designated as safety issue: No ]
  • Reactivity of T cells collected after transplantation [ Designated as safety issue: No ]
  • Pattern of post-transplantation CD14+ monocyte production of inflammatory cytokines, interleukin-1-alpha, and tumor necrosis factor alpha [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: December 2003
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Group 1 (allogeneic transplantation): Experimental
Patients receive donor 12-day cultured Th2 cells IV on day 1.
Biological: therapeutic allogeneic lymphocytes
Given IV
Group 2 (allogeneic transplantation): Experimental
Patients receive donor 12-day cultured Th2 cells IV on day 14. Patients also receive an initial loading dose of oral sirolimus once on day -2 and then oral sirolimus once daily on days -1 to 14.
Biological: therapeutic allogeneic lymphocytes
Given IV
Drug: sirolimus
Given orally
Group 3 (allogeneic transplantation): Experimental
Patients receive oral sirolimus as in group 2.
Drug: sirolimus
Given orally
Group 4 (allogeneic transplantation): Experimental
Patients receive donor 12-day or 6-day cultured Th2 cells and sirolimus as in group 2.
Biological: therapeutic allogeneic lymphocytes
Given IV
Drug: sirolimus
Given orally
Group 5 (allogeneic transplantation): Experimental
Patients receive donor 12-day cultured Th2 cells IV on day 0. Patients also receive sirolimus as in group 2.
Biological: therapeutic allogeneic lymphocytes
Given IV
Drug: sirolimus
Given orally

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histological diagnosis of 1 of the following hematologic malignancies, myelodysplasia, or myeloproliferative disorders:

    • Chronic lymphocytic leukemia

      • Relapsed after fludarabine
      • Non-complete remission (CR) after salvage regimen
    • Hodgkin's or non-Hodgkin's lymphoma (all types, including mantle cell lymphoma)

      • Primary treatment failure
      • Relapsed after autologous stem cell transplantation (SCT)
      • Non-CR after salvage regimen
    • High-risk lymphoma including, but not limited to, plasma dendritic cell type, hepato-splenic T cell type, gamma delta pinniculitic T cell type, muco-cutaneous NK cell type, or stage III-IV nasal NK cell type

      • Primary treatment failure
      • Relapsed after autologous SCT
      • Non-CR after salvage regimen
      • In first CR or any later CR
    • Multiple myeloma

      • Primary treatment failure
      • Relapsed after autologous SCT or for consolidation therapy after autologous SCT AND not yet relapsed
      • Non-CR after salvage regimen
    • Acute myeloid leukemia

      • In first CR (CR1) and at high risk [excludes t(8;21), t(15;17), or inv(16)]
      • In second CR (CR2) or greater
    • Acute lymphoblastic leukemia

      • In CR1 and at high risk [t(9;22) or bcr-abl+; t(4;11), 1(1;19), t(8;14)]
      • In CR2 or greater
    • Myelodysplastic syndromes

      • Refractory anemia with excess blasts (RAEB)
      • RAEB in transformation (requires bone marrow and blood blasts of less than 10% after induction chemotherapy)
    • Myeloproliferative disorders*

      • Idiopathic myelofibrosis
      • Polycythemia vera
      • Essential thrombocythemia
      • Chronic myelomonocytic leukemia NOTE: *Patients must be end-stage, primarily defined as disease severity refractory to splenectomy
    • Chronic myelogenous leukemia

      • Chronic phase refractory to imatinib mesylate
      • Accelerated phase
  • Acute leukemia must be in hematologic remission (less than 5% of blood or marrow blasts)
  • Must have a first-degree relative donor matched at 6/6 HLA antigens (A, B, and DR)
  • No active CNS involvement by malignancy

PATIENT CHARACTERISTICS:

Age

  • 18 to 75

Performance status

  • ECOG 0-1

Life expectancy

  • At least 3 months

Hematopoietic

  • Not specified

Hepatic

  • ALT and AST no greater than 2.5 times upper limit of normal*
  • Bilirubin less than 2.5 mg/dL* NOTE: *Values above these levels may be accepted, at the discretion of the principal investigator or study chairman, if the elevations are due to liver involvement

Renal

  • Creatinine no greater than 1.5 mg/dL
  • Creatinine clearance at least 50 mL/min

Cardiovascular

  • LVEF ≥ 45% by 2-dimensional ECHO or MUGA

    • Patients with LVEF between 35% and 44% are eligible provided they are cleared by a cardiology consultation that must include a cardiac stress test

Pulmonary

  • DLCO greater than 50% of expected

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 1 year after study participation
  • HIV negative
  • No active infection that is not responding to antimicrobial therapy
  • No psychiatric illness that would preclude study compliance or informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • No concurrent steroids as antiemetics during chemotherapy
  • No concurrent steroids during transplantation

Surgery

  • See Disease Characteristics

Other

  • At least 2 weeks since prior therapy and recovered
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077480

Locations
United States, Maryland
NCI - Center for Cancer Research Recruiting
Bethesda, Maryland, United States, 20892
Contact: Clinical Trials Office - NCI - Center for Cancer Research     888-624-1937        
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, New Jersey
Hackensack University Medical Center Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Clinical Trials Office - Hackensack University Medical Center     201-996-2879        
Sponsors and Collaborators
Investigators
Study Chair: Daniel Fowler, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided

Responsible Party: NCI - Center for Cancer Research ( Daniel Fowler )
Study ID Numbers: CDR0000350350, NCI-04-C-0055
Study First Received: February 10, 2004
Last Updated: October 10, 2009
ClinicalTrials.gov Identifier: NCT00077480     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
graft versus host disease
refractory chronic lymphocytic leukemia
accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
relapsing chronic myelogenous leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
chronic idiopathic myelofibrosis
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 mantle cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult lymphoblastic lymphoma
secondary myelodysplastic syndromes
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
chronic myelomonocytic leukemia
polycythemia vera
essential thrombocythemia
myelodysplastic/myeloproliferative disease, unclassifiable
recurrent marginal zone lymphoma

Additional relevant MeSH terms:
Sirolimus
Anti-Infective Agents
Immunologic Factors
Precancerous Conditions
Hematologic Neoplasms
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Antibiotics, Antineoplastic
Hemostatic Disorders
Anti-Bacterial Agents
Leukemia
Preleukemia
Neoplasms by Site
Pathologic Processes
Hemorrhagic Disorders
Antifungal Agents
Therapeutic Uses
Syndrome
Cardiovascular Diseases
Lymphoma
Disease
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Vascular Diseases

ClinicalTrials.gov processed this record on November 27, 2009