Know Cancer

or
forgot password

Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Aplastic Anemia


Phase 2
5 Years
75 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Thank you

Trial Information

Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Aplastic Anemia


OBJECTIVES:

- Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood
stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.

- Determine clinical response and overall outcome of patients treated with this regimen.

- Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism
in patients treated with this regimen.

OUTLINE:

- Preparative regimen:

- Matched related and unrelated donor transplantation:

- Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and
fludarabine IV over 30 minutes on days -5 to -1.

- Cord blood transplantation:

- Patients receive the same regimen as above plus anti-thymocyte globulin IV
over 4 hours on days -3 to -1.

- Graft-vs-host disease (GVHD) prophylaxis:

- Matched related and unrelated donor transplantation:

- Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate
mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of
this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.

NOTE: *This regimen is tapered from days 30-60 if donor chimerism of T-cells is 100%. MMF is
then stopped and tacrolimus is tapered by 25% every 10 days and discontinued by day 90 if no
GVHD develops.

- Cord blood transplantation:

- Patients receive tacrolimus and MMF in the same regimen as above plus
methylprednisolone twice daily on days 1-19 or until blood counts recover.

- Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or
peripheral blood stem cell transplantation on day 0. Patients then receive
sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing
until blood counts recover.

- Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell
chimerism by day 120 and showing signs of progresson of disease after
tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3
infusions. Cord blood recipients do not receive DLI.

Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months
for 5 years.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7
years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of aplastic anemia

- Severe disease

- Failed at least 1 course of standard immunosuppressive regimen with cyclosporine
and anti-thymocyte globulin OR

- Histologically confirmed hematologic malignancy including the following:

- Acute leukemia

- Any of the following types:

- Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes

- Secondary AML

- AML with high-risk cytogenetic abnormalities

- Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities

- Resistant or recurrent disease after combination chemotherapy with at least
1 standard regimen OR

- In first remission at high risk of relapse

- Chronic myelogenous leukemia

- Chronic phase meeting at least 1 of the following criteria:

- Failed imatinib mesylate

- Failed interferon after at least 6 months of treatment with minimum of
21 million units of interferon per week

- Unable to tolerate interferon

- Accelerated phase (blasts less than 20%)

- Myeloproliferative and myelodysplastic syndromes

- Myelofibrosis (after splenectomy)

- Refractory anemia

- Refractory anemia with excess blasts

- Chronic myelomonocytic leukemia

- Lymphoproliferative disease

- Chronic lymphocytic leukemia

- Symptomatic disease after first-line chemotherapy

- Low-grade non-Hodgkin's lymphoma (recurrent or persistent)

- Symptomatic disease after first-line chemotherapy

- Multiple myeloma

- Progressive disease after autologous stem cell transplantation

- Waldenstrom's macroglobulinemia

- Failed 1 standard regimen

- Non-Hodgkin's lymphoma meeting the following criteria:

- Intermediate or high grade

- Controlled and chemosensitive disease

- First remission lymphoblastic or small non-cleaved cell lymphoma at high
risk of relapse

- Hodgkin's lymphoma

- Relapsed and chemosensitive disease

- Not eligible for standard myeloablative allogeneic stem cell transplantation

- Availability of any of the following donor types:

- Related donor matched at 5 or 6 HLA antigens (A, B, DR)

- Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci

- Single antigen mismatch at C allowed

- Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE:
No syngeneic donors permitted

- No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification
scheme for adult non-Hodgkin's 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:

Age

- 5 to 75 (if related donor transplantation)

- 5 to 60 (if unrelated donor transplantation)

Performance status

- Karnofsky > 50%

Life expectancy

- Not specified

Hematopoietic

- Not specified

Hepatic

- Bilirubin less than 3 times normal

- Alkaline phosphatase less than 3 times normal

- AST/ALT less than 3 times normal

- No Child's class B or C liver failure

Renal

- Creatinine clearance greater than 40 mL/min

Cardiovascular

- Cardiac ventricular ejection fraction at least 35% by MUGA

- No cardiovascular disease

Pulmonary

- DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV antibody negative

- No uncontrolled diabetes mellitus

- No active serious infection

- No other disease that would preclude study therapy

- No other concurrent malignancy except non-melanoma skin cancer

- No concurrent serious psychiatric illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- At least 6 months since prior autologous bone marrow transplantation (BMT)

- At least 12 months since prior allogeneic BMT

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- At least 4 weeks since prior radiotherapy

Surgery

- At least 4 weeks since prior surgery

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Safety

Outcome Time Frame:

Weekly while on study

Safety Issue:

Yes

Principal Investigator

Philip L. McCarthy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000269673

NCT ID:

NCT00053989

Start Date:

January 2002

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • accelerated phase chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • primary myelofibrosis
  • de novo myelodysplastic syndromes
  • chronic phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • refractory anemia with excess blasts
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Waldenstrom macroglobulinemia
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • recurrent adult Hodgkin lymphoma
  • adult acute myeloid leukemia in remission
  • secondary acute myeloid leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • childhood acute lymphoblastic leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • noncontiguous stage II adult lymphoblastic lymphoma
  • refractory multiple myeloma
  • refractory anemia
  • refractory chronic lymphocytic leukemia
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • grade 1 follicular lymphoma
  • grade 2 follicular lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • recurrent adult acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • childhood acute myeloid leukemia in remission
  • childhood chronic myelogenous leukemia
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • childhood myelodysplastic syndromes
  • Anemia
  • Anemia, Aplastic
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263