A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

NCT ID: NCT01384513

Last Updated: 2022-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-04
• Study Completion Date: 2022-11-16

Brief Summary

The purpose of this research study is to compare the survival rates of patients with better risk disease undergoing hematopoietic stem cell transplant (HSCT) to the survival rates reported in the medical literature of similar patients undergoing reduced intensity HSCT from matched related donors.

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the overall survival (OS) rate at 2 years post treatment using the Jefferson 2 step reduced intensity conditioning (RIC) approach in patients with haploidentical family donors with hematological malignancies in morphological or radiographic remission or with chemosensitive, indolent diseases to historical OS rates in similar populations after RIC matched donor HSCT as reported in the literature.

SECONDARY OBJECTIVES:

I. To compare the treatment-related mortality (TRM) rate at 2 years for patients treated on this study to the historical TRM rates of patients undergoing RIC matched-sibling HSCT as reported in the literature.

II. To compare the 2 year relapse rates and relapse related mortality of patients with myeloid diseases to that of patients with lymphoid diseases who are treated on this Thomas Jefferson University (TJU) RIC 2 step approach.

III. To determine the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing treated on the TJU RIC 2 step approach.

IV. To evaluate engraftment rates and lymphoid reconstitution in patients treated on the TJU RIC 2 step approach.

V. To evaluate the incidence of TRM at 100 days in patients treated on the TJU RIC 2 step approach.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -11 to -8 and bulsufan IV over 3 hours on days -10 to -9. Patients undergo total body irradiation (TBI) on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo donor lymphocyte infusion (DLI) on day -6 and cluster of differentiation (CD)-34+ allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or orally (PO) with taper beginning on day 42. Patients also receive mycophenolate mofetil IV twice daily (BID) on days -1 to 28.

After completion of study treatment, patients are followed up periodically for 2 years.

Conditions

Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aplastic Anemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Mastocytosis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia

Study Design

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

Study Groups

Treatment (Allogeneic PBSCT)

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2.

TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0.

GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Given IV

Busulfan

Intervention Type: DRUG

Given IV

Total Body Irradiation (TBI)

Intervention Type: RADIATION

2 Gy administered as part of the conditioning regimen

Donor Lymphocyte Infusion (DLI)

Intervention Type: BIOLOGICAL

Undergo DLI

Cyclophosphamide (CY)

Intervention Type: DRUG

Given IV

Tacrolimus

Intervention Type: DRUG

Given IV or PO

Mycophenolate mofetil

Intervention Type: DRUG

Given IV

Allogeneic hematopoietic stem cell transplantation

Intervention Type: DEVICE

Undergo CD34+ allogeneic PBSCT

Peripheral blood stem cell transplantation (PBSCT)

Intervention Type: PROCEDURE

Undergo CD34+ allogeneic PBSCT

Interventions

Fludarabine

Given IV

Intervention Type: DRUG

Busulfan

Given IV

Intervention Type: DRUG

Total Body Irradiation (TBI)

2 Gy administered as part of the conditioning regimen

Intervention Type: RADIATION

Donor Lymphocyte Infusion (DLI)

Undergo DLI

Intervention Type: BIOLOGICAL

Cyclophosphamide (CY)

Given IV

Intervention Type: DRUG

Tacrolimus

Given IV or PO

Intervention Type: DRUG

Mycophenolate mofetil

Given IV

Intervention Type: DRUG

Allogeneic hematopoietic stem cell transplantation

Undergo CD34+ allogeneic PBSCT

Intervention Type: DEVICE

Peripheral blood stem cell transplantation (PBSCT)

Undergo CD34+ allogeneic PBSCT

Intervention Type: PROCEDURE

Other Intervention Names

fludarabine phosphate; Fludara; Myleran; Busulfex IV; radiotherapy; buffy coat fusion; Endoxan; Cytoxan; Neosar; Procytox; Revimmune; cytophosphane; FK-506; Fujimycin; MMF; CellCept; CliniMACS; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation; peripheral blood stem cell

Eligibility Criteria

Inclusion Criteria

1. Any patient with hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive.

2. Patients treated on this study will have:

• Acute leukemia in 1st or 2nd CR
• MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or RARS (refractory anemia with ringed sideroblasts) subtypes.
• Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease
• Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy
• Myeloproliferative disorders with at least a PR to current therapy
• Aplastic Anemia
• A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR).

3. Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section).

4. Patients must adequate organ function:

• LVEF (Left ventricular end diastolic function) of >50%
• DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin
• Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
• Creatinine Clearance of ≥ 60 mL/min

5. Performance status ≥ 80% (TJU Karnofsky) for patients ≥ 60 years old or ≥70% for patients < 60 years old.

6. HCT-CI Score ≤ 4 points for patients ≥ 60 years old or ≤ 5 points for patients < 60 years old.

7. Patients must be willing to use contraception if they have childbearing potential

8. Able to give informed consent

Exclusion Criteria

1. Performance status < 80% (TJU Karnofsky) for patients ≥ 60 years old or <70% for patients < 60.

2. Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) Score > 4 points for patients ≥ 60 years old or > 5 points for patients < 60.

3. HIV positive

4. Active involvement of the central nervous system with malignancy

5. Inability to obtain informed consent

6. Pregnancy

7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder

8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit anti-thymocyte globulin and have an anti-thymocyte globulin level of > 2 ugm/ml

9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Cancer Center at Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dolores Grosso, DNP, CRNP

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Cancer Center at Thomas Jefferson University

Neal Flomenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Cancer Center at Thomas Jefferson University

Locations

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Countries

United States

Related Links

http://www.KimmelCancerCenter.org

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center

http://www.JeffersonHospital.org

Thomas Jefferson University Hospitals

Other Identifiers

2011-31

Identifier Type: OTHER

Identifier Source: secondary_id

11D.247

Identifier Type: -

Identifier Source: org_study_id