Know Cancer

or
forgot password

Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Thank you

Trial Information

Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan


OBJECTIVES:

- To assess the efficacy and toxicity of reduced-intensity allogeneic peripheral blood
stem cell transplantation in patients with hematological malignancies treated with
conditioning therapy comprising fludarabine phosphate and busulfan.

- To evaluate progression-free survival and overall survival in patients treated with
this regimen.

- To determine donor chimerism.

- To access the risk of acute and chronic graft-versus-host-disease (GVHD) in patients
treated with this regimen.

OUTLINE:

- Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and
fludarabine phosphate IV over 30 minutes on days -6 to -2.

- Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic
PBSC on day 0.

- Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients
achieve100% donor T-cell chimerism on day 30 without disease recurrence, and
cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1
to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every
12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.

Patients with recurrent disease or < 100% donor T-cell chimerism (on day 30) undergo a
12-day CSA and MMF taper followed by escalating doses of previously collected donor
leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in
the absence of ≥ grade 2 GVHD.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosed with any of the following:

- Acute myeloid leukemia (AML), meeting 1 of the following criteria:

- Recurrent disease in remission, defined as morphological remission with
bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of
study treatment (cytogenetic or molecular remission is not required)

- In first complete remission (CR1) with poor-risk cytogenetics, antecedent
hematological disease (i.e., myelodysplasia), or treatment-related leukemia

- Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

- Recurrent disease in remission, defined as morphological remission with
bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of
study treatment (cytogenetic or molecular remission is not required)

- CR1 with Philadelphia chromosome or poor-risk cytogenetics

- Chronic myelogenous leukemia (CML), meeting the following criteria:

- First or second chronic phase

- Must be documented disease progression after imatinib mesylate therapy
OR documented lack of cytogenetic response 6 months post-imatinib
mesylate initiation OR imatinib mesylate intolerance

- Chronic lymphocytic leukemia (CLL), meeting the following criteria:

- Recurrent disease after fludarabine-based therapy

- Must have chemosensitive disease at the time of relapse, defined as
greater than 50% reduction of WBC and lymphadenopathy

- Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-,
intermediate-, or high-grade disease*), or transformed NHL, meeting 1 of the
following criteria:

- Received prior autologous transplantation and cytoreductive therapy at the
time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu)
as defined by the International Workshop

- Relapsed disease that required more than 2 salvage regimens to achieve CR
or CRu

- Recurrent multiple myeloma, meeting the following criteria:

- Must have received prior autologous transplantation and demonstrate
chemosensitivity at the time of relapse, defined as greater than 50%
reduction of M-component or plasma-cell marrow infiltration

- Myelodysplastic syndrome

- Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory
cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with
multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with
excess blasts (RAEB) I, meeting the following criteria:

- Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on
WHO criteria

- No RAEB II or del(5q)

- No uncontrolled CNS metastases

- 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor)
available NOTE: *A new classification scheme for adult non-Hodgkin 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:

- Karnofsky performance status ≥ 50%

- Serum creatinine ≤ 2 mg/dL

- Not pregnant

- Fertile patients must use effective contraception

- 50 years of age or older

- Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

- Have a preexisting medical condition

- Received prior therapy (i.e., autologous transplantation) and are
considered to be too high risk for conventional myeloablative
transplantation

- Must be willing to accept or comprehend irreversible sterility as a side effect of
therapy

- No uncontrolled active infection

- No psychiatric illness or mental deficiency making compliance with treatment or
informed consent impossible

- Cardiac ejection fraction ≥ 30%

- Corrected pulmonary-diffusing capacity ≥ 35%

- No serologic evidence of infection with HIV

- No decompensated liver disease with serum bilirubin > 2.0 mg/dL

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Day 100 transplant-related mortality

Outcome Time Frame:

Up to 2 years

Safety Issue:

Yes

Principal Investigator

Carol M. Richman, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Davis

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000583059

NCT ID:

NCT00619645

Start Date:

June 2007

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • recurrent adult acute myeloid leukemia
  • adult acute lymphoblastic leukemia in remission
  • refractory anemia with excess blasts
  • refractory anemia with ringed sideroblasts
  • refractory anemia
  • refractory cytopenia with multilineage dysplasia
  • previously treated myelodysplastic syndromes
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia in remission
  • 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)
  • chronic phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • recurrent adult Hodgkin lymphoma
  • refractory multiple myeloma
  • recurrent adult acute lymphoblastic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • secondary acute myeloid leukemia
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic 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
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • recurrent adult lymphoblastic lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent adult Burkitt lymphoma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • de novo myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

University of California Davis Cancer CenterSacramento, California  95817