Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers

• ClinicalTrials.gov Identifier: NCT00619645
• Recruitment Status: Completed
• First Posted: February 21, 2008
• Results First Posted: May 8, 2017
• Last Update Posted: January 10, 2018
• Sponsor: University of California, Davis
• Information provided by (Responsible Party): University of California, Davis

Study Description

Brief Summary:

Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.

Condition or disease	Intervention/treatment	Phase
Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes	Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description:

OUTLINE:

• Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
• Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
• Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.

Patients with recurrent disease or < 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan
• Study Start Date: June 2007
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

Arm	Intervention/treatment
RIST for Heme malignancies; Busulfan 3.3 mg/kg over 3 hours on day -6 and day -5 Fludarabine 30 mg/m2 IV over 30 minutes on day -6 to day -2 followed by Transplant followed by Immunosuppressive/GVHD therapy	Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures :

1. Number of Patients With Day 100 Transplant-related Mortality [ Time Frame: 24 months after day 100 transplant ]
   Patients were followed for death and whether or not that death was attributed to the day 100 transplant via physician assessment for 24 months after day 100 transplant.

Secondary Outcome Measures :

1. Number of Patients Without Progression After Day 100 Transplant [ Time Frame: 24 months after day 100 transplant ]
   All patients will be followed for progression for 24 months after their day 100 transplant.
2. Number of Patients Alive 24 Months Post Day 100 Transplant [ Time Frame: 24 months post day 100 transplant ]
   Patients will be followed for survival for 24 months post day 100 transplant.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Diagnosed with any of the following:

  • Acute myeloid leukemia (AML), meeting 1 of the following criteria:

    • Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    • In first complete remission (CR1) with poor-risk cytogenetics, antecedent hematological disease (i.e., myelodysplasia), or treatment-related leukemia

  • Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

    • Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    • CR1 with Philadelphia chromosome or poor-risk cytogenetics

  • Chronic myelogenous leukemia (CML), meeting the following criteria:

    • First or second chronic phase

      • Must be documented disease progression after imatinib mesylate therapy OR documented lack of cytogenetic response 6 months post-imatinib mesylate initiation OR imatinib mesylate intolerance

  • Chronic lymphocytic leukemia (CLL), meeting the following criteria:

    • Recurrent disease after fludarabine-based therapy

      • Must have chemosensitive disease at the time of relapse, defined as greater than 50% reduction of WBC and lymphadenopathy

  • Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-, intermediate-, or high-grade disease*), or transformed NHL, meeting 1 of the following criteria:

    • Received prior autologous transplantation and cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop
    • Relapsed disease that required more than 2 salvage regimens to achieve CR or CRu

  • Recurrent multiple myeloma, meeting the following criteria:

    • Must have received prior autologous transplantation and demonstrate chemosensitivity at the time of relapse, defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration

  • Myelodysplastic syndrome

    • Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess blasts (RAEB) I, meeting the following criteria:

      • Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on WHO criteria
      • No RAEB II or del(5q)
• No uncontrolled CNS metastases
• 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor) available

PATIENT CHARACTERISTICS:

• Karnofsky performance status ≥ 50%
• Serum creatinine ≤ 2 mg/dL
• Not pregnant
• Fertile patients must use effective contraception

• 50 years of age or older

  • Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

    • Have a preexisting medical condition
    • Received prior therapy (i.e., autologous transplantation) and are considered to be too high risk for conventional myeloablative transplantation
• Must be willing to accept or comprehend irreversible sterility as a side effect of therapy
• No uncontrolled active infection
• No psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
• Cardiac ejection fraction ≥ 30%
• Corrected pulmonary-diffusing capacity ≥ 35%
• No serologic evidence of infection with HIV
• No decompensated liver disease with serum bilirubin > 2.0 mg/dL

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Contacts and Locations

Locations

United States, California

University of California Davis Cancer Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

• Study Chair: Carol M. Richman, MD; University of California, Davis

More Information

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00619645
• Other Study ID Numbers: UCDCC#196; 288263 ( Other Identifier: UC Davis ); UCD-196 ( Other Identifier: UCDCC )
• First Posted: February 21, 2008
• Results First Posted: May 8, 2017
• Last Update Posted: January 10, 2018
• Last Verified: January 2018

Keywords provided by University of California, Davis:

recurrent adult acute myeloid leukemia; adult acute lymphoblastic leukemia in remission; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; refractory cytopenia with multilineage dysplasia; previously treated myelodysplastic syndromes; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia in remission; 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); chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; refractory multiple myeloma; recurrent adult acute lymphoblastic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; secondary acute myeloid leukemia; recurrent small lymphocytic lymphoma; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma

Additional relevant MeSH terms:

Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Syndrome; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease; Pathologic Processes; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Bone Marrow Diseases; Precancerous Conditions; Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Busulfan