Clinical trial NCT00304018: Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
Official title: Pilot Study of Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
refractory multiple myeloma
adult acute lymphoblastic leukemia in remission
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
stage II multiple myeloma
stage III multiple myeloma
recurrent adult acute lymphoblastic leukemia
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
recurrent adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
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)
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent adult T-cell leukemia/lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult Hodgkin lymphoma
stage IV adult T-cell leukemia/lymphoma
stage IV mantle cell lymphoma
stage III adult T-cell leukemia/lymphoma
stage I multiple myeloma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-03-17
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and etoposide, before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer 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 antithymocyte globulin before transplant and tacrolimus and prednisone after transplant may stop this from happening.

PURPOSE: This phase I trial is studying how well donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of \> 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

Secondary

* Determine the toxicity of a myeloablative preparative regimen comprising busulfan, fludarabine, and etoposide prior to UCBT in these patients.
* Determine the neutrophil and platelet recovery in patients treated with this regimen.
* Determine the event-free and overall survival of patients treated with this regimen.
* Evaluate lineage-specific chimerism after UCBT and assess the contribution of each individual cord blood unit to post-transplantation hematopoiesis in these patients.
* Determine the incidence, severity, and timing of acute and chronic graft-vs-host disease in patients treated with this regimen.

OUTLINE: This is a pilot study.

* Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours 4 times daily on days -7 and -4, etoposide IV over 4 hours on day -3, and anti-thymocyte globulin IV over 6 hours on days -2 and -1.
* Donor umbilical cord blood transplantation (UCBT): Patients undergo donor UCBT on day 0. Beginning on day 7, patients receive sargramostim (GM-CSF) IV or subcutaneously once daily until blood counts recover.
* Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally twice daily beginning on day -2 and continuing until day 180 followed by a taper. Patients also receive oral prednisone twice daily on days 13-50 and then once daily on days 50-60, followed by a rapid taper.

After completion of study treatment, patients are followed periodically for approximately 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following advanced hematologic malignancies:

  * Acute myeloid leukemia (AML) meeting the following criteria:

    * Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

      * High-risk cytogenetics (-7, -7q, -5, -5q, t\[6,9\], t\[9,11\], complex, Philadelphia chromosome positive \[Ph+\])
      * AML evolved from prior myelodysplasia
      * AML secondary to prior chemotherapy
      * Failed to achieve remission
      * In second or subsequent remission
    * Marrow blasts ≤ 10% (may be achieved using chemotherapy)
  * Myelodysplastic syndromes (MDS) with high-risk features

    * International Prognostic Scoring System (IPSS) score intermediate -2 or high-risk
    * Marrow blasts ≤ 20% (may be achieved using chemotherapy)
  * Acute lymphoblastic leukemia meeting the following criteria:

    * Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:

      * High-risk cytogenetics (Ph+, t\[4,11\], 11q23 abnormalities, and monosomy 7)
      * Required \> 1 induction course to achieve remission
      * Failed to achieve remission
      * In second or subsequent remission
    * Marrow blasts ≤ 10% (may be achieved using chemotherapy)
  * Chronic myelogenous leukemia meeting ≥ 1 of the following criteria:

    * Accelerated phase
    * Chronic phase refractory to imatinib mesylate
    * Blastic phase

      * Marrow blasts ≤ 10% (may be achieved using chemotherapy)
  * Multiple myeloma meeting 1 of the following criteria:

    * Stage II or III disease with \> first relapse or refractory disease
    * Newly diagnosed disease with chromosome 13 abnormalities
  * Lymphoma meeting the following criteria:

    * One of the following subtypes:

      * Diffuse large cell lymphoma
      * Mantle cell lymphoma
      * Peripheral T-cell lymphoma
      * T-natural killer (NK) cell lymphoma
      * Hodgkin's lymphoma
    * Disease failed to respond to primary therapy, progressed, or recurred after prior therapy

      * Patients who have failed autologous stem cell transplantation are eligible provided it has been \> 1 year since transplant
* No rapid progression of malignant disease
* Not eligible for autologous stem cell transplantation
* Available umbilical cord blood (1-3 units) donor matching at ≥ 4 of 6 HLA antigens (A, B, and DR)

  * Patients with an HLA-identical or 1 antigen-mismatched related donor OR a potential HLA-matched unrelated donor matching at \> 6/8 (A, B, C, DR) alleles are not eligible

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Creatinine \< 2.0 mg/dL
* Creatinine clearance \> 40 mL/min
* Bilirubin \< 2.0 mg/dL
* AST and alkaline phosphatase \< 3 times upper limit of normal
* Hepatitis C and active hepatitis B allowed if patient has ≤ grade 2 inflammation or fibrosis by liver biopsy
* Ejection fraction \> 40% by echocardiogram or MUGA
* DLCO \> 40% of predicted
* Not pregnant or nursing
* Negative pregnancy test
* No known HIV infection
* No active infection requiring ongoing antibiotic treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies
timeFrame: up to 24 months post-transplant
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Thomas G. Martin, MD
role: STUDY_CHAIR
References: