Clinical trial · Interventional

Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

A Pilot Phase II Study of Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation

NCT01116232CI-TRIAL-00037812terminatedPhase 2Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Why stopped (as posted): Lack of funding.

Summary

Brief summary (as posted)

This Phase II clinical trial was designed for patients with hematologic malignancies in need of donor peripheral blood stem cell transplant, and have no HLA matched donor. Therefore It will test the efficacy of combining sirolimus, tacrolimus, antithymocyte globulin, and rituximab in preventing graft versus host disease in transplants from HLA Haploidentical and partially mismatched donors.

Conditions

Conditions (8)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Chronic Myeloproliferative Disorders	Myeloproliferative Neoplasm	ALIAS	0.90
Graft Versus Host Disease	—	UNRESOLVED	—
Leukemia	Leukemia	ONTOLOGY_EXACT	0.90
Lymphoma	Lymphoma	ONTOLOGY_EXACT	0.90
Lymphoproliferative Disorder	—	UNRESOLVED	—
Multiple Myeloma and Plasma Cell Neoplasm	—	UNRESOLVED	—
Myelodysplastic/Myeloproliferative Neoplasms	Myelodysplastic/Myeloproliferative Neoplasm	CURATED_BROADER	0.80
Myelodysplastic Syndromes	Myelodysplastic Syndrome

Interventions

Interventions (8)

Intervention	Type	Mapped drug	Match
allogeneic hematopoietic stem cell transplantation	Procedure	—	UNRESOLVED
anti-thymocyte globulin	Biological	—	UNRESOLVED
laboratory biomarker analysis	Other	—	UNRESOLVED
management of therapy complications	Procedure	—	UNRESOLVED
peripheral blood stem cell transplantation	Procedure	—	UNRESOLVED
rituximab	Biological	Rituximab	ALIAS
sirolimus	Drug	Sirolimus	ALIAS
tacrolimus	Drug	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
anti-thymocyte globulin, rituximab, sirolimus, tacrolimus,
description
anti-thymocyte globulin: Infuse the first dose over a minimum of 6 hours, and subsequent doses over a minimum of 4 hours via a 0.22 micron in-line filter Rituximab: The total dose chosen for this protocol is 28 mg/kg divided in two doses (14 mg/kg on days -7 and +3). Initial infusion: Start rate of 50 mg/hour; For adults, Sirolimus will be administered at 12 mg orally loading dose on day -3, followed by 4 mg orally single morning daily dose (target serum level 3-12 ng/ml by HPLC). Tacrolimus will be administered intravenously at a dose of 0.03 mg/kg (ideal body weight) q 24h by continuous infusion starting on Day -3. Intravenous Tacrolimus will be discontinued once the patient starts eating and the drug will then be given orally at a dose of approximately 4 times the intravenous dose.
interventionNames
1. Biological: anti-thymocyte globulin
2. Biological: rituximab
3. Drug: sirolimus
4. Drug: tacrolimus
5. Other: laboratory biomarker analysis
6. Procedure: allogeneic hematopoietic stem cell transplantation
7. Procedure: management of therapy complications
8. Procedure: peripheral blood stem cell transplantation

Primary outcomes (3)

measure

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 120 Years

Show eligibility criteria text

DISEASE CHARACTERISTICS:

* Diagnosis of a hematological malignancy, including:

  * Non-Hodgkin lymphoma
  * Hodgkin lymphoma
  * Acute myeloid leukemia or acute lymphoblastic leukemia
  * Myelodysplastic syndrome (treated or untreated)
  * Chronic myelogenous leukemia
  * Multiple myeloma
  * Chronic lymphocytic leukemia
  * Myelofibrosis and other myeloproliferative disorders
* No suitable related HLA-matched or unrelated HLA-matched (8/8 or 7/8 matched) donor
* Available suitable haploidentical or partial-matched unrelated donor (high-resolution molecular HLA typing is mandatory for HLA Class I and II)

  * No more than 4/8 HLA allele or antigen mismatch for a haploidentical-related first-degree family member donor
  * Only 6/8 or 5/8 allele or antigen match for an unrelated donor
* Scheduled to undergo peripheral blood stem cell transplantation

  * Not receiving bone marrow or ex vivo engineered or processed graft (e.g., CD34+ enrichment, T-cell depletion)
* No documented uncontrolled CNS disease

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 70-100%
* ECOG PS 0-2
* Serum bilirubin \< 3 times upper limit of normal (ULN)
* ALT and AST \< 3 times ULN
* Creatinine clearance \> 60 mL/min
* Ejection fraction \> 50%
* Forced vital capacity, FEV\_1, or DLCO \> 50% predicted
* Negative pregnancy test
* Able to cooperate with oral medication intake
* Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the past 6 months) are eligible provided they are cleared with a stress echo or nuclear myocardial perfusions stress test and a cardiology consult
* No ascites
* No HIV positivity
* No active hepatitis B or C virus infection
* No known contraindication to the administration of sirolimus, tacrolimus, anti-thymocyte globulin, or rituximab

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Not on home oxygen

References

Publications (0)

Data not yet available

No reference posted for this study.

Registry

Dates and enrollment