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Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia


Phase 2/Phase 3
4 Years
70 Years
Open (Enrolling)
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases, Nonmalignant Neoplasm, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia


OBJECTIVES:

- Compare the morbidity, mortality, and overall outcome of patients with severe aplastic
anemia or hematologic malignancy treated with standard vs novel conditioning regimens
followed by allogeneic stem cell transplantation.

- Examine the influence of donor histocompatibility on outcome by comparing
matched/related, mismatched/related (with or without T-cell depletion), and
matched/unrelated transplants with stratification for type of preparative regimen.

- Ensure that patients with uncommon diagnoses will be treated in a uniform fashion with
the best therapy available.

OUTLINE: Patients are stratified according to risk of relapse (standard-risk: acute leukemia
in first complete remission, chronic myelogenous leukemia in first chronic phase, lymphoma
in sensitive first relapse or second remission, primary or untreated myelodysplastic
syndromes, or untreated severe aplastic anemia vs high-risk: all others).

Patients are assigned to one of the following conditioning regimens based on diagnosis, risk
of relapse, and donor relatedness:

- Regimen 1: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and
cyclophosphamide IV over 2 hours on days -3 and -2.

- Regimen 2: Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and
anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.

- Regimen 3: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and
total-body irradiation (TBI) twice daily on days -3 to -1.

- Regimen 4: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and
melphalan IV over 1 hour on days -3 and -2.

- Regimen 5: Patients receive etoposide IV over 26 hours beginning on day -5,
cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.

- Regimen 6: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24
hours, and thiotepa IV over 24 hours on days -7 to -4.

- Regimen 7: Patients receive fludarabine IV over 30 minutes on days -5 to -1 and
anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.

- Regimen 8: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI
twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3
to -1.

- Regimen 9: Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte
globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on
days -3 and -2.

All patients then receive donor stem cell infusions on day 0. Some patients may undergo
involved-field radiotherapy 4-8 weeks after transplant.

Patients are followed periodically post-transplant.

PROJECTED ACCRUAL: At least 405 patients will be accrued for this study within 5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of one of the following:

- Severe aplastic anemia as defined by either of the following:

- Marrow cellularity (< 25% [or 25-50% cellularity with < 30% of remaining
cells hematopoietic in origin])

- At least 2 of the following abnormal peripheral blood counts:

- Reticulocyte count < 1% (corrected for hematocrit)

- Platelet count < 20,000/mm^3

- Neutrophil count < 500/mm^3

- Histologically confirmed hematologic malignancy, including any of the following:

- Acute leukemia

- Resistant or recurrent disease after combination chemotherapy with at
least one standard regimen OR in first remission and at high risk of
relapse

- Acute myeloid leukemia (AML) (antecedent myelodysplastic syndromes
[MDS], secondary AML, or high-risk cytogenetic abnormalities)

- Acute lymphoblastic leukemia (ALL) (high-risk cytogenetic
abnormalities)

- Chronic myeloid leukemia (CML)

- Chronic phase, accelerated phase, or blast phase

- Myeloproliferative disorders or MDS, including any of the following:

- Myelofibrosis

- Polycythemia vera*

- Essential thrombocythemia*

- Refractory anemia

- Refractory anemia with excess blasts

- Refractory anemia with excess blasts in transformation

- Chronic myelomonocytic leukemia NOTE: * Only if transformed to AML or
MDS

- Lymphoproliferative disease

- Recurrent or persistent, symptomatic disease after first-line
chemotherapy, including any of the following:

- Chronic lymphocytic leukemia (CLL) (≥ 20% marrow involvement)

- Waldenstrom macroglobulinemia

- Low-grade non-Hodgkin lymphoma

- Intermediate or high-grade non-Hodgkin lymphoma, meeting 1 of the following
criteria:

- Resistant or recurrent disease after combination chemotherapy with one
standard regimen

- Lymphoblastic lymphoma or small noncleaved cell lymphoma in first
remission and at high risk of relapse

- CNS disease

- Bone marrow disease and LDH greater than 300

- Solid tumor that would otherwise be treated on RPCI-DS-9115 (or equivalent
autologous stem transplant protocol) AND has a syngeneic donor

- Autologous bone marrow transplant not possible (or desirable) due to 1 of the
following:

- History of marrow tumor

- Inadequate marrow dose

- Abnormal marrow histology or function prior to storage

- Thrombocytopenia or leukopenia

- Marrow cellularity < 20%

- Histocompatible donor identified

- Well-matched donor, as defined by 1 of the following:

- Family member matched for 5 or 6 HLA specificities (A, B, DR)*

- Unrelated donor meeting compatibility criteria of the National Marrow Donor
Program (matched for HLA A, B, and DRB1 antigens)*

- Identical twin sibling

- If a compatible cord blood donor is identified and there is no suitable
unrelated donor available, patient may receive cord blood transplant NOTE:
*Patients ≤ 25 years of age may be singly mismatched at the A or B loci

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:

- 4 to 70

Performance status:

- Zubrod 0-2 OR

- Karnofsky 70-100%

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- Bilirubin < 3 times normal (unless due to disease)

- Alkaline phosphatase < 3 times normal (unless due to disease)

- SGOT < 3 times normal (unless due to disease)

- Hepatitis B surface antigen negative

- No severe hepatic disease that would preclude study participation

Renal:

- Creatinine normal

- Creatinine clearance ≥ 50 mL/min

- No severe renal disease that would preclude study participation

Cardiovascular:

- Cardiac ventricular ejection fraction ≥ 50% by MUGA or echocardiogram

- No uncontrolled or severe cardiovascular disease (e.g., myocardial infarction,
congestive heart failure, symptomatic angina, life threatening arrhythmia, or
hypertension within the past 6 months)

Pulmonary:

- DLCO or DLVA ≥ 50% predicted (corrected for hemoglobin or alveolar ventilation)

Other:

- No serious concurrent medical or psychiatric illness

- No other serious organ dysfunction (unless due to underlying disease), including the
following:

- Uncontrolled bacterial, viral, or fungal infection

- Uncontrolled peptic ulcer disease

- Uncontrolled diabetes mellitus

- HIV negative

- Cytomegalovirus status known

- Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- See Disease Characteristics

- Pretransplant cytoreductive chemotherapy allowed for patients with relapsed or
refractory disease

Endocrine therapy:

- Not specified

Radiotherapy:

- Not eligible for total-body irradiation if prior radiotherapy exceeded the following
limits:

- Mediastinum: 3,600 cGy

- Heart: 3,600 cGy

- Whole lungs: 1,200 cGy

- Small bowel: 3,600 cGy

- Kidneys: 1,200 cGy

- Whole liver: 1,600 cGy

- Cranial spinal: 3,600 cGy

- Brain: 4,000 cGy

- Retina: 4,000 cGy

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Activity of allogeneic stem cell transplant

Outcome Time Frame:

day 100

Safety Issue:

No

Principal Investigator

Philip L. McCarthy, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000066968

NCT ID:

NCT00003816

Start Date:

October 1998

Completion Date:

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • Nonmalignant Neoplasm
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • Burkitt lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • adult acute myeloid leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • polycythemia vera
  • essential thrombocythemia
  • refractory anemia
  • refractory anemia with excess blasts
  • refractory anemia with excess blasts in transformation
  • chronic myelomonocytic leukemia
  • T-cell large granular lymphocyte leukemia
  • acute undifferentiated leukemia
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • secondary acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • prolymphocytic leukemia
  • intraocular lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent mantle cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • anaplastic large cell lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • primary myelofibrosis
  • 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
  • aplastic anemia
  • unspecified adult solid tumor, protocol specific
  • unspecified childhood solid tumor, protocol specific
  • Anemia
  • Anemia, Aplastic
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263