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A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies


N/A
N/A
69 Years
Open (Enrolling)
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Precancerous Condition, Secondary Myelofibrosis

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Trial Information

A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies


OBJECTIVES:

Primary

- Determine the efficacy of double umbilical cord blood stem cell transplantation using a
conditioning regimen comprising lower doses of busulfan and fludarabine phosphate and
low-dose total body irradiation, in terms of stem cell engraftment at 60 days post
transplantation, in patients with hematologic cancer or other diseases.

- Determine the merits of conducting a larger, comparative study of this regimen.

Secondary

- Determine mortality within 100 days of transplantation in these patients.

OUTLINE: This is a pilot study.

- Reduced-intensity conditioning regimen: Patients receive busulfan IV over 3 hours on
days -9 to -8 and fludarabine phosphate IV on days -7 to -3. Patients then undergo
low-dose total body irradiation on day 0.

- Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV twice daily and
mycophenolate orally or IV three times daily beginning on day -3.

- CNS prophylaxis and/or treatment: Patients with a history of CNS involvement receive
prophylactic cytarabine (Ara-C) intrathecally (IT) prior to transplant. Patients also
undergo lumbar puncture (LP) to test for active CNS disease. Patients with
cerebrospinal fluid positive for leukemia receive Ara-C IT every 2-3 days until a
repeat LP shows no remaining leukemic cells. Three days after the last LP and after one
final dose of Ara-C, patients begin the conditioning regimen.

- Double umbilical cord blood (UCB) donor stem cell transplantation (SCT): Patients
undergo double UCB donor SCT on day 0.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Acute myeloid leukemia meeting the following criteria:

- M0-M7 histologic subtypes by French-American-British classification

- Previously treated disease

- Meets 1 of the following criteria:

- Persistent disease as evidenced by 5-30% persistent blasts in bone
marrow after induction or salvage therapy

- In second or subsequent complete remission (CR)

- In first CR with 1 of the following high-risk features:

- Philadelphia chromosome present

- Noncore-binding factor type of chromosomal abnormalities

- Myelodysplastic syndromes with 1 of the following International Prognostic
Scoring System (IPSS) scores:

- Intermediate-1

- Intermediate-2

- High-risk score with transfusion dependence

- Chronic myelogenous leukemia meeting 1 of the following criteria:

- In accelerated or blastic phase

- Failed prior imatinib mesylate therapy

- Acute lymphoblastic leukemia meeting 1 of the following criteria:

- In first CR with any of the following high-risk features:

- Philadelphia chromosome present

- Translocation t(4;11) present

- WBC > 30,000/mm³ (adult patients)

- More than 4 weeks from initiation of treatment was required to achieve
CR (adult patients)

- DNA index of near haploid (N=23 chromosomes) (pediatric patients)

- In second or subsequent CR

- Persistent disease as evidenced by 5-20% persistent blasts in bone marrow
after induction or salvage therapy

- Hodgkin's or non-Hodgkin's lymphoma meeting the following criteria:

- Recurrent or refractory disease

- Tumor ≤ 5 cm in diameter

- Myeloma or plasma cell neoplasm meeting 1 of the following staging criteria:

- Stage III at presentation

- Stage I-II at presentation

- Not responding OR progressed after first-line therapy

- Chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia with refractory
or progressive disease after first-line therapy

- No 5-6/6 HLA-matched related or 7-8/8 HLA-matched unrelated marrow or peripheral
blood stem cell donor available

- No single 4-6/6 HLA-A, -B, or -DRB1-matched umbilical cord blood unit ≥ 3.5 x 10^7
nucleated cells/kg available

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky or Lansky PS 70-100%

- Not pregnant

- Fertile patients must use effective contraception prior to and during study
participation

- HIV negative

- Bilirubin < 3.0 mg/dL

- AST and ALT ≤ 3 times upper limit of normal

- Creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min

- Cardiac ejection fraction > 50% by echocardiogram OR shortening fraction > 27%

- No uncontrolled symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- FEV_1 > 50% of normal

- Forced vital capacity > 50% of normal

- DLCO normal

- Oxygen saturation > 92% on room air (for patients < 5 years of age)

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to busulfan and fludarabine phosphate

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior and no concurrent surgery

- At least 4 weeks since prior and no other concurrent investigational or commercial
agents or therapies for the malignancy, including chemotherapy, biologic therapy, or
radiotherapy

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Engraftment

Outcome Time Frame:

60 days post transplantation

Safety Issue:

No

Principal Investigator

Voravit Ratanatharathorn, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000518230

NCT ID:

NCT00423826

Start Date:

January 2007

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Precancerous Condition
  • Secondary Myelofibrosis
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • childhood acute lymphoblastic leukemia in remission
  • recurrent childhood acute lymphoblastic leukemia
  • adult acute myeloid leukemia in remission
  • 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)
  • recurrent adult acute myeloid leukemia
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute promyelocytic leukemia (M3)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • adult acute megakaryoblastic leukemia (M7)
  • childhood acute myeloblastic leukemia without maturation (M1)
  • childhood acute myeloblastic leukemia with maturation (M2)
  • childhood acute promyelocytic leukemia (M3)
  • childhood acute myelomonocytic leukemia (M4)
  • childhood acute monoblastic leukemia (M5a)
  • childhood acute monocytic leukemia (M5b)
  • childhood acute erythroleukemia (M6)
  • childhood acute megakaryocytic leukemia (M7)
  • childhood acute myeloid leukemia in remission
  • secondary myelodysplastic syndromes
  • recurrent childhood acute myeloid leukemia
  • refractory chronic lymphocytic leukemia
  • recurrent adult Hodgkin lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • adult grade III lymphomatoid granulomatosis
  • adult nasal type extranodal NK/T-cell lymphoma
  • Waldenstrom macroglobulinemia
  • 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 grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent marginal zone lymphoma
  • secondary acute myeloid leukemia
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • extramedullary plasmacytoma
  • isolated plasmacytoma of bone
  • monoclonal gammopathy of undetermined significance
  • primary systemic amyloidosis
  • refractory multiple myeloma
  • de novo myelodysplastic syndromes
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • childhood grade III lymphomatoid granulomatosis
  • childhood nasal type extranodal NK/T-cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • Burkitt lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • previously treated myelodysplastic syndromes
  • splenic marginal zone lymphoma
  • recurrent childhood grade III lymphomatoid granulomatosis
  • recurrent adult lymphoblastic lymphoma
  • recurrent small lymphocytic lymphoma
  • secondary myelofibrosis
  • Primary Myelofibrosis
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Precancerous Conditions
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201