NMA Allogeneic Hematopoietic Cell Transplant in Hematologic Cancer/Disorders

Lymphoma Clinical Trial

Official title:

Non-Myeloablative Allogeneic Hematopoietic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053989
• Other study ID #: CDR0000269673
• Secondary ID: RP01-05
• Status: Completed
• Phase: Phase 2
• Start date: January 29, 2002
• Est. completion date: July 19, 2018

Study information

• Verified date: December 2019
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 19, 2018
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 75 Years

Eligibility

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

• 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

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia
• Chronic Myeloproliferative Disorders
• Fanconi Anemia
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Neoplasms, Plasma Cell
• Preleukemia
• Syndrome

Intervention

Biological:
• anti-thymocyte globulin
iv
• graft-versus-tumor induction therapy
iv
• sargramostim
iv
• therapeutic allogeneic lymphocytes
iv

Drug:
• cyclophosphamide
injection
• fludarabine phosphate
iv
• methylprednisolone
oral
• mycophenolate mofetil
oral
• tacrolimus
oral

Procedure:
• allogeneic bone marrow transplantation
iv
• peripheral blood stem cell transplantation
iv
• umbilical cord blood transplantation
iv

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Day 100 TRM	treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0	from start or conditioning (day -6 or -5) through day +100 after HSC infusion
Primary	Day 100 Best Response	Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol	from start of conditioning on day -6 or -5 through day +100 after HSC infusion
Secondary	PFS	Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion	1 year
Secondary	OS	Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion	1 year
Secondary	Acute GvHD	overall grade II-IV acute GvHD	Day +100