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Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide


Phase 1
N/A
70 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide


OBJECTIVES:

- Determine the minimum effective dose of pretransplant cyclophosphamide to induce
engraftment of haploidentical allogeneic bone marrow without the use of myeloablative
conditioning in patients with hematologic malignancies.

- Determine the incidence and severity of graft versus host disease and nonhematologic
toxicities with this treatment regimen in these patients.

- Correlate the pretreatment phenotypic and functional immunologic characteristics in
these patients in relation to risk of graft rejection with this treatment regimen.

OUTLINE: This is a dose-escalation study of cyclophosphamide.

Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1
hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow
transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days
4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV
starting on day 4 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum
effective dose necessary to induce chimerism without unacceptable toxicity in these patients
is determined.

Patients are followed at 2 and 6 months, at one year, and then annually thereafter.

PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Patients with any of the following diagnoses:

- Chronic myelogenous leukemia

- Chronic phase 1

- Failed prior interferon alfa therapy OR

- Relapsed after prior autologous stem cell transplantation

- Chronic phase 2

- Acute leukemia

- Standard risk

- Age over 60 years

- Complete remission 1 (CR1)

- High risk

- High WBC at presentation, unfavorable cytogenetics, mixed lineage,
delayed response to induction chemotherapy

- CR1

- Complete remission 2 or higher

- Acute lymphocytic leukemia

- CR1 or higher

- Myelodysplastic syndrome

- Untreated OR

- CR1

- Acute myeloid leukemia in CR1

- Chronic lymphocytic leukemia

- Rai stage III or IV OR

- Received prior autologous stem cell transplantation

- Multiple myeloma

- Stage II or III

- Stable or progressive disease after prior chemotherapy OR

- Received prior autologous stem cell transplantation

- Non-Hodgkin's Lymphoma

- Hodgkin's lymphoma

- Ineligible for or refused autologous or standard allogeneic bone marrow
transplantation

- Ineligible for bone marrow transplantation from an HLA matched, sibling donor or from
an HLA matched, unrelated donor

- Must have an HLA mismatched, related donor (3-5 out of 6)

PATIENT CHARACTERISTICS:

Age:

- 0.5 to 70

Performance status:

- ECOG 0-1

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Bilirubin less than 3.1 mg/dL

Renal:

- Not specified

Cardiovascular:

- Left ventricular ejection fraction at least 35%

Pulmonary:

- FEV_1 and FVC at least 40% of predicted OR

- FEV_1 and FVC at least 60% in patients who have received prior thoracic or mantle
radiotherapy

Other:

- HIV negative

- No other debilitating medical or psychiatric illness that would preclude study
compliance

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- No prior transfusions from donor

Chemotherapy:

- See Disease Characteristics

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Ephraim J. Fuchs, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000068057, J9966

NCT ID:

NCT00006042

Start Date:

December 1999

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • recurrent adult Hodgkin lymphoma
  • Burkitt lymphoma
  • refractory multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • recurrent childhood lymphoblastic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • relapsing chronic myelogenous leukemia
  • refractory chronic lymphocytic leukemia
  • chronic 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
  • recurrent/refractory childhood Hodgkin lymphoma
  • stage II adult lymphoblastic lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV adult Burkitt lymphoma
  • 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
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • childhood chronic myelogenous leukemia
  • atypical chronic myeloid leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage III marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone 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
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410