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Protocol Details

Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

07-C-0195

Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 74

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Unrelated Donors;
Reduced Intensity Stem Cell Transplant;
Leukemia;
Lymphoma;
Allogeneic Stem Cell Transplant

Recruitment Keyword(s)

Lymphoma;
Leukemia;
Myelodysplastic Syndrome;
Multiple Myeloma

Condition(s)

Myelodysplastic Syndrome;
Hodgkin's Lymphoma;
Non-Hodgkin's Lymphoma;
Acute Leukemia;
Multiple Myeloma

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: Rituximab
Drug: Cyclosporine
Drug: Allogenic stem cell transplant (ASCT)
Drug: Conditioning Chemotherapy
Drug: TMS
Drug: FLAG
Drug: EPOCH-F
Biological/Vaccine: Alemtuzumab

Supporting Site

National Cancer Institute

Background:

Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without an HLA tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patient s immune system attacks the transplanted donor cells.

This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.

Objectives:

To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.

To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

-Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continuing through day 14 following SCT.

-Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donor s stem cells and immune cells 2 days after the conditioning regimen.

Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.

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Eligibility

ELIGIBILITY CRITERIA RECIPIENT ON STANDARD CARE THERAPY:

-The patient is 18 74 years of age.

-The patient has a potentially suitable 8/8 donor if they are between the ages of 69-74 years of age or a potentially suitable 8/8 or 7/8 unrelated donor(s) in the National Marrow Registry or Other Available Registry if they are between the ages of 18-74.

-The patient currently does not meet the protocol s eligibility/enrollment criteria for any reason.

-There is a high likelihood that the patient, in the opinion of the PI or LAI, will meet the protocol s eligibility/enrollment criteria to proceed to transplant after standard therapy is completed.

-The patient or legal guardian is able to give informed consent.

EXCLUSION CRITERIA RECIPIENT ON STANDARD CARE THERAPY:

-HIV infection. There is theoretical concern that the degree of immune suppression associated with the treatment may result in progression of HIV infection.

-Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. The effects of the chemotherapy, the subsequent transplant and the medications used after the transplant are highly likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to the infant.


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Citations:

Pavletic SZ, Martin P, Lee SJ, Mitchell S, Jacobsohn D, Cowen EW, Turner ML, Akpek G, Gilman A, McDonald G, Schubert M, Berger A, Bross P, Chien JW, Couriel D, Dunn JP, Fall-Dickson J, Farrell A, Flowers ME, Greinix H, Hirschfeld S, Gerber L, Kim S, Knobler R, Lachenbruch PA, Miller FW, Mittleman B, Papadopoulos E, Parsons SK, Przepiorka D, Robinson M, Ward M, Reeve B, Rider LG, Shulman H, Schultz KR, Weisdorf D, Vogelsang GB; Response Criteria Working Group. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006 Mar;12(3):252-66.

Shaffer BC, Modric M, Stetler-Stevenson M, Arthur DC, Steinberg SM, Liewehr DJ, Fowler DH, Gale RP, Bishop MR, Pavletic SZ. Rapid complete donor lymphoid chimerism and graft-versus-leukemia effect are important in early control of chronic lymphocytic leukemia. Exp Hematol. 2013 Sep;41(9):772-8. doi: 10.1016/j.exphem.2013.04.015. Epub 2013 May 18.

Pavletic SZ, Lee SJ, Socie G, Vogelsang G. Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials. Bone Marrow Transplant. 2006 Nov;38(10):645-51. Epub 2006 Sep 18.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Steven Z. Pavletic, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3130
10 CENTER DR
BETHESDA MD 20892
(240) 760-6174
sp326h@nih.gov

Steven Z. Pavletic, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-3130
10 CENTER DR
BETHESDA MD 20892
(240) 760-6174
sp326h@nih.gov

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
1-888-NCI-1937

Clinical Trials Number:

NCT00520130

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