Donor Bone Marrow Transplant in Treating Patients With Leukemia, Lymphoma, or Nonmalignant Hematologic Disorders

Allogeneic Bone Marrow Transplantation Using Closely Matched Related and Unrelated Donors

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related or unrelated donor, that closely matches the patient's blood, are infused into the patient they may help the patient's bone marrow to make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in treating patients with leukemia, lymphoma, or nonmalignant hematologic disorders.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Leukemia; Chronic Myeloproliferative Disorders; Myelodysplastic/Myeloproliferative Neoplasms; Multiple Myeloma and Malignant Plasma Cell Neoplasms
• Intervention / Treatment: Drug: cyclophosphamide; Radiation: TBI

Detailed Description

OBJECTIVES:

• Determine the survival of allogeneic bone marrow transplantation using closely matched related and unrelated donors in patients with malignant or nonmalignant hematological disorders.
• Determine the incidence and severity of acute and chronic graft versus host disease with this treatment regimen in these patients.
• Determine the relapse rates with this treatment regimen in those patients with malignant disorders.
• Determine the incidence and severity of infectious complications associated with this treatment regimen in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -6 and -5, total body radiotherapy on days -3 through 0, and allogeneic bone marrow transplantation on day 0.

Patients with acute lymphocytic leukemia (ALL) receive intrathecal methotrexate at the beginning of the study. If CNS involvement is documented, patients receive a second dose of methotrexate 48 hours later followed by oral leucovorin calcium every 6 hours for 4 doses. Patients with ALL and/or CNS involvement receive intrathecal methotrexate every other week for 12 weeks after transplant.

Patients with prior CNS involvement receive radiotherapy for 2.5 weeks prior to transplant. Patients with ALL receive total body radiotherapy for 5 consecutive days prior to transplant.

Patients are followed once a week for 3 months, and then monthly for 1 year.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study over 6 years.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of one of the following:

  • Acute lymphocytic leukemia (ALL):

    • Complete remission (CR) 1 - high risk defined as overt CNS involvement or poor cytogenetics (additions, deletions, translocations, or multiple abnormalities)
    • CR2
    • Induction failures
    • Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt

  • Acute myelogenous leukemia (AML):

    • CR1 - high risk defined as poor cytogenetics (deletions, additions, multiple abnormalities)
    • CR2
    • Induction failures
    • Relapse - patients with at least 10% marrow blasts undergo at least one reinduction attempt

  • Chronic myelogenous leukemia (CML):

    • Chronic phase (CP) 1
    • Accelerated phase/CP2 - patients in blast phase must undergo treatment and achieve a second chronic phase prior to transplant

  • Chronic lymphocytic leukemia (CLL):

    • Relapse - any stage; must have received no more than 3 prior regimens

  • Multiple myeloma:

    • At diagnosis - primary refractory
    • Relapse (no more than 2) - sensitive disease
    • Plasma cell leukemia
    • Inability to achieve a complete remission after autologous transplant (no older than 40)
  • Myelodysplasia - all subtypes
  • Myeloproliferative disorders - patients with poor response to medical therapy or cytogenetic abnormalities

  • Severe aplastic anemia (SAA):

    • Very SAA - at diagnosis
    • SAA - induction therapy
• Donors must be a phenotypic (6 out of 6) match or a one antigen (A or B) mismatch

PATIENT CHARACTERISTICS:

Age:

• 15 to 50

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT and SGPT no greater than 3 times normal
• PT/PTT normal

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• Left ventricular ejection fraction at least 45%
• No myocardial infarction within past 6 months
• No uncontrolled arrhythmias

Pulmonary:

• FEV1 at least 50%
• DLCO at least 50% predicted

Other:

• No active serious infection
• HIV negative
• Not pregnant or nursing
• No uncontrolled diabetes mellitus or thyroid disease

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cy/TBI; cyclophosphamide and total body irradiation (TBI)	Drug: cyclophosphamide; Cyclophosphamide is administered at a dose of 60 mg/kg on each of two successive days (Days -6 and -5); Radiation: TBI; FTBI is performed on day -3 through day 0 The total dose of radiation is 1,320 cGy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event free survival (EFS)	EFS determined by the Kaplan-Meier product limit method	five year post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of graft versus host disease	incidence and severity of acute and chronic GVHD	five years post transplant

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: May 1, 1996
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: May 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): October 25, 2012
• Last Update Submitted That Met QC Criteria: October 24, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: primary myelofibrosis; stage I chronic lymphocytic leukemia; refractory anemia; refractory anemia with ringed sideroblasts; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; chronic phase chronic myelogenous leukemia; childhood myelodysplastic syndromes; recurrent adult acute myeloid leukemia; adult acute myeloid leukemia in remission; blastic phase chronic myelogenous leukemia; stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; refractory multiple myeloma; recurrent adult acute lymphoblastic leukemia; polycythemia vera; essential thrombocythemia; recurrent childhood acute lymphoblastic leukemia; accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; recurrent childhood acute myeloid leukemia; myelodysplastic/myeloproliferative neoplasm, unclassifiable; chronic eosinophilic leukemia; chronic neutrophilic leukemia; atypical chronic myeloid leukemia, BCR-ABL1 negative; refractory cytopenia with multilineage dysplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Disease; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Precancerous Conditions; Neoplasms; Syndrome; Myelodysplastic Syndromes; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia; Preleukemia; Plasmacytoma; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: MCC-11282; IRB-4189 (Other Identifier: University of South Florida IRB); NCI-G00-1755 (Other Identifier: NCI)