Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer or Aplastic Anemia - Full Text View

Sponsor:	Roswell Park Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00053989

Purpose

RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood 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 system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Biological: graft-versus-tumor induction therapy Biological: sargramostim Biological: therapeutic allogeneic lymphocytes Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methylprednisolone Drug: mycophenolate mofetil Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Procedure: umbilical cord blood transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Aplastic Anemia

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Anemia Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Methylprednisolone Tacrolimus anhydrous Tacrolimus Mycophenolate mofetil hydrochloride Sargramostim Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Toxicity [ Designated as safety issue: Yes ]
Clinical response [ Designated as safety issue: No ]
Overall outcome [ Designated as safety issue: No ]
Incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	January 2002
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
Determine clinical response and overall outcome of patients treated with this regimen.
Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.

OUTLINE:

Preparative regimen:
- Matched related and unrelated donor transplantation:
  - Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
- Cord blood transplantation:
  - Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.
Graft-vs-host disease (GVHD) prophylaxis:
- Matched related and unrelated donor transplantation:
  - Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.

NOTE: *This regimen is tapered from days 30-60 if donor chimerism of T-cells is 100%. MMF is then stopped and tacrolimus is tapered by 25% every 10 days and discontinued by day 90 if no GVHD develops.

Cord blood transplantation:
- Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.
  - Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  - Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.

Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.

Eligibility

Ages Eligible for Study:	5 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of aplastic anemia
- Severe disease
- Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin OR
Histologically confirmed hematologic malignancy including the following:
- Acute leukemia
  - Any of the following types:
    - Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes
    - Secondary AML
    - AML with high-risk cytogenetic abnormalities
    - Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities
  - Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR
  - In first remission at high risk of relapse
- Chronic myelogenous leukemia
  - Chronic phase meeting at least 1 of the following criteria:
    - Failed imatinib mesylate
    - Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week
    - Unable to tolerate interferon
  - Accelerated phase (blasts less than 20%)
- Myeloproliferative and myelodysplastic syndromes
  - Myelofibrosis (after splenectomy)
  - Refractory anemia
  - Refractory anemia with excess blasts
  - Chronic myelomonocytic leukemia
- Lymphoproliferative disease
  - Chronic lymphocytic leukemia
    - Symptomatic disease after first-line chemotherapy
  - Low-grade non-Hodgkin's lymphoma (recurrent or persistent)
    - Symptomatic disease after first-line chemotherapy
  - Multiple myeloma
    - Progressive disease after autologous stem cell transplantation
  - Waldenstrom's macroglobulinemia
    - Failed 1 standard regimen
- Non-Hodgkin's lymphoma meeting the following criteria:
  - Intermediate or high grade
  - Controlled and chemosensitive disease
  - First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse
- Hodgkin's lymphoma
  - Relapsed and chemosensitive disease
Not eligible for standard myeloablative allogeneic stem cell transplantation
Availability of any of the following donor types:
- Related donor matched at 5 or 6 HLA antigens (A, B, DR)
- Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci
  - Single antigen mismatch at C allowed
- Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted
No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

5 to 75 (if related donor transplantation)
5 to 60 (if unrelated donor transplantation)

Performance status

Karnofsky > 50%

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin less than 3 times normal
Alkaline phosphatase less than 3 times normal
AST/ALT less than 3 times normal
No Child's class B or C liver failure

Renal

Creatinine clearance greater than 40 mL/min

Cardiovascular

Cardiac ventricular ejection fraction at least 35% by MUGA
No cardiovascular disease

Pulmonary

DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV antibody negative
No uncontrolled diabetes mellitus
No active serious infection
No other disease that would preclude study therapy
No other concurrent malignancy except non-melanoma skin cancer
No concurrent serious psychiatric illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
At least 6 months since prior autologous bone marrow transplantation (BMT)
At least 12 months since prior allogeneic BMT

Chemotherapy

See Disease Characteristics
At least 4 weeks since prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

At least 4 weeks since prior radiotherapy

Surgery

At least 4 weeks since prior surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053989

Locations

United States, New York
Roswell Park Cancer Institute	Recruiting
Buffalo, New York, United States, 14263-0001
Contact: Clinical Trials Office - Roswell Park Cancer Institute 877-275-7724

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Philip L. McCarthy, MD

Roswell Park Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Roswell Park Cancer Institute ( Philip L. McCarthy, Jr )
Study ID Numbers:	CDR0000269673, RPCI-RP-0105
Study First Received:	February 5, 2003
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00053989 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

accelerated phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic idiopathic myelofibrosis
de novo myelodysplastic syndromes
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory anemia with excess blasts
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Waldenstrom macroglobulinemia
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage III adult Burkitt lymphoma

stage IV adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma
adult acute myeloid leukemia in remission
secondary acute myeloid leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
childhood acute lymphoblastic leukemia in remission
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
noncontiguous stage II adult lymphoblastic lymphoma
refractory multiple myeloma
refractory anemia
refractory chronic lymphocytic leukemia
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Mycophenolic Acid
Antiemetics
Tacrolimus
Hormones
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses

Mycophenolate mofetil
Cardiovascular Diseases
Methylprednisolone Hemisuccinate
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Glucocorticoids
Multiple Myeloma
Neoplasms
Fludarabine
Antimetabolites
Vidarabine
Precancerous Conditions

ClinicalTrials.gov processed this record on November 27, 2009