Study of Low-Intensity Conditioning for Allogeneic Stem Cell Transplant

NCT00143845 | Completed Phase 2 Results DMC

• 1 other identifier: UMCC 2-61
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether a reduced intensity conditioning regimen for stem cell transplant with donor cells will allow the donor cells to be effective without causing health problems.

Conditions

Multiple Myeloma; Lymphocytic Leukemia, Chronic; Lymphoma, Low-Grade

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Acute Graft Versus Host Disease (GVHD) Grades 2-4

  The primary objective of this study was to establish the rate of acute GVHD following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. Glucksberg staging was used for organ grading of GVHD. Clinical GVHD was assessed as follows: Grade 0: No stage 1-4 of any organ Grade 1: Stage 1-2 rash and no liver or gut involvement Grade 2: Stage 3 rash, or Stage 1 liver involvement, or Stage 1 GI Grade 3: Stage 0-3 skin with Stage 2-3 liver, or Stage 2-4 GI Grade 4: Stage 4 skin rash, or Stage 4 liver involvement

  100 days

• Percentage of Participants With Progression Free Survival

  The second primary objective was to determine the percentage of participants with progression free survival following prophylactic cellular immunotherapy after allogeneic hematopoietic stem cell therapy using low intensity conditioning for high-risk hematological malignancies. We define disease progression as disease recurrence within 180 days of transplant.

  two years

Secondary Outcomes (1)

• Percentage of Patients Alive at 2 Years

  2 Years

Study Arms (1)

Immunosuppression Taper

EXPERIMENTAL

Reduced intensity conditioning consisting of Busulfan and Fludarabine(fludarabine 150 mg/m2 IV, busulfan 6 mg/kg IV, total lymphoid irradiation 2 Gy), followed by a rapid immunosuppressive taper of Tacrolimus (0.06 mg/kg q12h, PO, Days -7 to +28), Methotrexate (5 mg/m2, IV, Days +1, +3, +6, +11) and Mycophenolate Mofetil (10 mg/kg every 8 hours, PO, Days -6 to +7).

Procedure: Reduced intensity conditioning; Procedure: Rapid immunosuppressive taper; Procedure: Prophylactic donor leukocyte infusions

Interventions

Reduced intensity conditioning PROCEDURE

Busulfan and Fludarabine regimen

Immunosuppression Taper

Rapid immunosuppressive taper PROCEDURE

Taper of Tacrolimus, Methotrexate and Mycophenolate Mofetil

Immunosuppression Taper

Prophylactic donor leukocyte infusions PROCEDURE

If the patient has GVHD overall grade 0-1 or skin grade 1 on day +100, then 5 x 107 CD3+ cells/kg recipient weight are given.

Immunosuppression Taper

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible a patient MUST meet at least one of the next 4 criteria
• Any patient aged 55 years or older with a hematological malignancy for which allogeneic transplant is considered an appropriate treatment, AND/OR
• Any patient, regardless of age, with a hematologic malignancy for which allogeneic transplant is considered an appropriate treatment and the patient is not eligible for a conventional myeloablative transplant because of organ dysfunction AND/OR
• Any patient, regardless of age, who has relapsed following prior autologous or allogeneic transplant for a hematologic malignancy AND/OR
• Any patient, regardless of age, with one of the following hematological malignancies:
• Multiple myeloma
• refractory to or failure following conventional chemotherapy such as VAD (Vincristine, Adriamycin and Dexamethasone), pulse decadron, or alkylating agents, or
• chromosomal abnormality associated with poor prognosis by cytogenetics or FISH probe.
• Chronic lymphocytic leukemia patients, Rai stage 3 or 4 and relapsed following/refractory to alkylating agents or nucleoside analog therapy
• Low grade lymphoma (small lymphocytic, follicular small cleaved cell, or follicular mixed small cleaved and large cell) that is either relapsed or refractory provided the disease is NOT rapidly progressive, NOT bulky, and no mass exceeds 5 cm in greatest dimension.
• To be eligible a patient MUST meet all of the following criteria
• In addition to the above criteria ALL patients must meet the following minimum organ function:
• Cardiac: Ejection fraction at least 30%.
• Renal: Adequate renal function as defined by creatinine \< 2.0mg OR creatinine clearance \>40 mg/min by 24-hour urine collection or GFR (Glomerular Filtration Rate. (Gender and age-adjusted creatinine clearance \>40ml/min by Gault-Cockroft 55 is acceptable for adults: (140 - age) x weight/72 x Scr \[x 0.85 if female\]).
• Pulmonary: FEV1 and FVC \>60%.

You may not qualify if:

• acute leukemia
• HIV positive patients not eligible
• Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient
• Pregnant
• /6 or 6/6 HLA match for HLA-A, B, and DR
• Age 3-70 years, good general health
• No contraindication to G-CSF (Granulocyte Colony-Stimulating Factor)stimulation
• No contraindication to leukapheresis of peripheral blood stem cells
• Good general health
• HIV positive or history of HIV risk factors
• Presence of other diseases transmissible by blood that pose unacceptable risk to the study subject.
• Pregnant
• Medical or psychological conditions that would make the donor unlikely to tolerate G-CSF - injections or leukapheresis

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

The University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Results Point of Contact

• Title: Dr. John Levine, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

jelevine@umich.edu

734-936-8456

Study Officials

• John E. Levine, MD, MS

  The Univeristy of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2005
• First Posted: September 2, 2005
• Study Start: April 1, 2003
• Primary Completion: November 1, 2010
• Study Completion: February 1, 2013
• Last Updated: March 8, 2017
• Results First Posted: June 20, 2014

Record last verified: 2017-01

Locations

US (1)