Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006042
• Other study ID #: CDR0000068057, J9966
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 1
• First received: July 5, 2000
• Last updated: March 9, 2010
• Start date: December 1999

Study information

• Verified date: March 2010
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase I trial to study the effectiveness of cyclophosphamide plus bone marrow transplantation in treating patients who have hematologic cancer.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 70 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Biological:
• filgrastim

Drug:
• cyclophosphamide

• fludarabine phosphate

• mycophenolate mofetil

• tacrolimus

Procedure:
• allogeneic bone marrow transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blo — View Citation