Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Study Description

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Brief Summary:

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal 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 or abnormal 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 tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well umbilical cord blood stem cell transplant works in treating patients with hematologic cancer or other disease.

Condition or disease	Intervention/treatment
Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Secondary Myelofibrosis	Drug: Busulfan; Drug: Cytarabine; Drug: Fludarabine phosphate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation; Radiation: total-body irradiation

Detailed Description:

OBJECTIVES:

Primary

• Determine the efficacy of double umbilical cord blood stem cell transplantation using a conditioning regimen comprising lower doses of busulfan and fludarabine phosphate and low-dose total body irradiation, in terms of stem cell engraftment at 60 days post transplantation, in patients with hematologic cancer or other diseases.
• Determine the merits of conducting a larger, comparative study of this regimen.

Secondary

• Determine mortality within 100 days of transplantation in these patients.

OUTLINE: This is a pilot study.

• Reduced-intensity conditioning regimen: Patients receive busulfan IV over 3 hours on days -9 to -8 and fludarabine phosphate IV on days -7 to -3. Patients then undergo low-dose total body irradiation on day 0.
• Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV twice daily and mycophenolate orally or IV three times daily beginning on day -3.
• CNS prophylaxis and/or treatment: Patients with a history of CNS involvement receive prophylactic cytarabine (Ara-C) intrathecally (IT) prior to transplant. Patients also undergo lumbar puncture (LP) to test for active CNS disease. Patients with cerebrospinal fluid positive for leukemia receive Ara-C IT every 2-3 days until a repeat LP shows no remaining leukemic cells. Three days after the last LP and after one final dose of Ara-C, patients begin the conditioning regimen.
• Double umbilical cord blood (UCB) donor stem cell transplantation (SCT): Patients undergo double UCB donor SCT on day 0.

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

Study Design

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Study Type :	Expanded Access
Official Title:	A Pilot Study of Double Cord Blood Stem Cell Transplantation in Patients With Hematologic Malignancies
Study Start Date :	January 2007
Actual Primary Completion Date :	January 2015
Actual Study Completion Date :	January 2015

Interventions

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Intervention Details:

Drug: Busulfan
3 mg/kg intravenously over 3 hours
Other Names:
• Busulfex®
• Myleran®
Drug: Cytarabine
Patients with previous history of CNS involvement will receive pre-transplant intrathecal Cytarabine (Ara-C) (30 mg/M2) therapy.
Other Names:
• DepoCyt(TM)
• Liposomal Ara-C
Drug: Fludarabine phosphate
25 mg/M2/day IV
Other Name: Fludara
Drug: mycophenolate mofetil
Orally at the dose of 1 gm every 8 hours.
Other Name: Cellcept
Drug: tacrolimus
0.015 mg/kg IV every 12 hours by continuous infusion.
Other Names:
• Advagraf
• Prograf
• Protopic
Procedure: allogeneic hematopoietic stem cell transplantation
10 days post drug intervention
Procedure: umbilical cord blood transplantation
10 days post drug intervention
Radiation: total-body irradiation
10 days post drug intervention

Eligibility Criteria

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Ages Eligible for Study:	up to 69 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

  • Acute myeloid leukemia meeting the following criteria:

    • M0-M7 histologic subtypes by French-American-British classification
    • Previously treated disease

    • Meets 1 of the following criteria:

      • Persistent disease as evidenced by 5-30% persistent blasts in bone marrow after induction or salvage therapy
      • In second or subsequent complete remission (CR)

      • In first CR with 1 of the following high-risk features:

        • Philadelphia chromosome present
        • Noncore-binding factor type of chromosomal abnormalities

  • Myelodysplastic syndromes with 1 of the following International Prognostic Scoring System (IPSS) scores:

    • Intermediate-1
    • Intermediate-2
    • High-risk score with transfusion dependence

  • Chronic myelogenous leukemia meeting 1 of the following criteria:

    • In accelerated or blastic phase
    • Failed prior imatinib mesylate therapy

  • Acute lymphoblastic leukemia meeting 1 of the following criteria:

    • In first CR with any of the following high-risk features:

      • Philadelphia chromosome present
      • Translocation t(4;11) present
      • WBC > 30,000/mm³ (adult patients)
      • More than 4 weeks from initiation of treatment was required to achieve CR (adult patients)
      • DNA index of near haploid (N=23 chromosomes) (pediatric patients)
    • In second or subsequent CR
    • Persistent disease as evidenced by 5-20% persistent blasts in bone marrow after induction or salvage therapy

  • Hodgkin's or non-Hodgkin's lymphoma meeting the following criteria:

    • Recurrent or refractory disease
    • Tumor ≤ 5 cm in diameter

  • Myeloma or plasma cell neoplasm meeting 1 of the following staging criteria:

    • Stage III at presentation

    • Stage I-II at presentation

      • Not responding OR progressed after first-line therapy
  • Chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia with refractory or progressive disease after first-line therapy
• No 5-6/6 HLA-matched related or 7-8/8 HLA-matched unrelated marrow or peripheral blood stem cell donor available
• No single 4-6/6 HLA-A, -B, or -DRB1-matched umbilical cord blood unit ≥ 3.5 x 10^7 nucleated cells/kg available

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky or Lansky PS 70-100%
• Not pregnant
• Fertile patients must use effective contraception prior to and during study participation
• HIV negative
• Bilirubin < 3.0 mg/dL
• AST and ALT ≤ 3 times upper limit of normal
• Creatinine < 2.0 mg/dL OR creatinine clearance > 50 mL/min
• Cardiac ejection fraction > 50% by echocardiogram OR shortening fraction > 27%
• No uncontrolled symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• FEV_1 > 50% of normal
• Forced vital capacity > 50% of normal
• DLCO normal
• Oxygen saturation > 92% on room air (for patients < 5 years of age)
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to busulfan and fludarabine phosphate
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior and no concurrent surgery
• At least 4 weeks since prior and no other concurrent investigational or commercial agents or therapies for the malignancy, including chemotherapy, biologic therapy, or radiotherapy

Contacts and Locations

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Locations

United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:	Voravit Ratanatharathorn, MD	Barbara Ann Karmanos Cancer Institute

More Information

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Responsible Party:	Voravit Ratanatharathorn, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00423826 History of Changes
Other Study ID Numbers:	CDR0000518230; P30CA022453 ( U.S. NIH Grant/Contract ); WSU-2006-059 ( Other Identifier: Barbara Ann Karmanos Cancer Institute ); WSU-112506MP2F ( Other Identifier: Wayne State University Institutional Review Board )
First Posted:	January 18, 2007
Last Update Posted:	February 29, 2016
Last Verified:	February 2016

Keywords provided by Voravit Ratanatharathorn, Barbara Ann Karmanos Cancer Institute:

accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; childhood acute lymphoblastic leukemia in remission; recurrent childhood acute lymphoblastic leukemia; adult acute myeloid leukemia in remission; 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); recurrent adult acute myeloid leukemia

adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute promyelocytic leukemia (M3); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); childhood acute myeloblastic leukemia without maturation (M1); childhood acute myeloblastic leukemia with maturation (M2); childhood acute promyelocytic leukemia (M3); childhood acute myelomonocytic leukemia (M4); childhood acute monoblastic leukemia (M5a)

Additional relevant MeSH terms:

Lymphoma; Syndrome; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Preleukemia; Neoplasm Metastasis; Primary Myelofibrosis; Plasmacytoma; Precancerous Conditions; 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; Neoplastic Processes; Myeloproliferative Disorders; Tacrolimus