NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders

NCT ID: NCT00053989

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-29
• Study Completion Date: 2018-07-19

Brief Summary

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.

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.
• 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.

Conditions

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Fanconi Anemia; Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All patients

All patients enrolled on study

Group Type: EXPERIMENTAL

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

iv

graft-versus-tumor induction therapy

Intervention Type: BIOLOGICAL

iv

sargramostim

Intervention Type: BIOLOGICAL

iv

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

iv

cyclophosphamide

Intervention Type: DRUG

injection

fludarabine phosphate

Intervention Type: DRUG

iv

methylprednisolone

Intervention Type: DRUG

oral

mycophenolate mofetil

Intervention Type: DRUG

oral

tacrolimus

Intervention Type: DRUG

oral

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

iv

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

iv

umbilical cord blood transplantation

Intervention Type: PROCEDURE

iv

Interventions

anti-thymocyte globulin

iv

Intervention Type: BIOLOGICAL

graft-versus-tumor induction therapy

iv

Intervention Type: BIOLOGICAL

sargramostim

iv

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

iv

Intervention Type: BIOLOGICAL

cyclophosphamide

injection

Intervention Type: DRUG

fludarabine phosphate

iv

Intervention Type: DRUG

methylprednisolone

oral

Intervention Type: DRUG

mycophenolate mofetil

oral

Intervention Type: DRUG

tacrolimus

oral

Intervention Type: DRUG

allogeneic bone marrow transplantation

iv

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

iv

Intervention Type: PROCEDURE

umbilical cord blood transplantation

iv

Intervention Type: PROCEDURE

Other Intervention Names

FLUDARA

Eligibility Criteria

Inclusion Criteria

• 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

• 4 to 75 (if related or unrelated donor peripheral blood or marrow transplantation)
• 4 to 60 (if unrelated cord blood 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
• patients may have received a prior autologous blood or marrow transplantation (BMT)
• At least 6 months since prior allogeneic BMT

Chemotherapy

• See Disease Characteristics
• At least 2 weeks since prior chemotherapy, radiation or surgery

Endocrine therapy

• Not specified

Radiotherapy

• At least 2 weeks since prior radiotherapy

Surgery

• At least 2 weeks since prior surgery

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip L. McCarthy, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RP01-05

Identifier Type: -

Identifier Source: secondary_id

CDR0000269673

Identifier Type: -

Identifier Source: org_study_id